Approach to surgery following chemotherapy for advanced testicular germ cell tumors

INTRODUCTION — Testicular cancers, 95 percent of which are germ cell tumors (GCTs), are one of the most curable solid neoplasms. Cisplatin-based regimens can cure patients with advanced GCTs, even in the context of widespread visceral metastases, highly elevated serum tumor markers, or other adverse prognostic features. Following chemotherapy, the role of surgery depends on the histological type; for males with nonseminomatous germ cell tumors (NSGCTs), a multimodality approach of chemotherapy followed by resection of all residual masses when technically feasible is the standard of care. In contrast, advanced stage seminomas are often managed with chemotherapy alone; the resection (or biopsies) of residual masses are only performed under certain specific circumstances. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)

Males with rising tumor markers at the end of treatment have chemorefractory disease. In general, these patients should be treated with second-line systemic chemotherapy, although surgery may represent the patient's best chance of cure in selected cases [1]. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors".)

This topic will review the role of surgery after chemotherapy in males with advanced disease. A general overview of the treatment of testicular cancer and the role of retroperitoneal lymph node dissection for early stage GCT (primarily in relation to males with NSGCT) are presented separately. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors" and "Retroperitoneal lymph node dissection for early-stage testicular germ cell tumors".)

IMAGING OF RESIDUAL DISEASE — Following chemotherapy or radiation therapy (RT) for advanced germ cell tumor (GCT), all patients should undergo imaging, utilizing either high-resolution computed tomography (CT) or magnetic resonance imaging (MRI). The imaging characteristics of these masses differ by whether the primary tumor is a seminoma or a nonseminomatous germ cell tumor (NSGCT).

Seminoma — Following first-line imaging (CT or MRI), we often obtain a fluorodeoxyglucose (FDG) positron emission tomography (PET) scan if a residual mass ≥3 cm is identified. We suggest surgical resection for masses ≥3 cm that are FDG avid.

Residual masses are commonly seen after RT or chemotherapy for seminoma. Two radiologic patterns are usually described [2-7]:

●The retroperitoneal mass may have the appearance of a sheet of tissue around the great vessels, obliterating radiographic planes [8]. Such a mass tends to merge with the great vessels, psoas muscles, and other retroperitoneal structures. This appearance usually represents fibrosis and is often unresectable [9].

●Retroperitoneal masses may appear delineated and distinct from surrounding structures. Compared with the above pattern of radiographic abnormality, these masses are more likely to be resectable and often represent residual seminoma [9,10].

Following first-line imaging (CT or MRI), we often obtain an FDG-PET scan, particularly if a residual mass ≥3 cm is identified. The FDG-PET results are used to make surgical recommendations in these patients. The 3 cm cut-off is based on the results of the SEMinoma PET (SEMPET) trial that included 51 males treated for seminoma, all of whom had residual lesions postchemotherapy [11]. Using a size cut-off of 3 cm, PET had a specificity, sensitivity, positive predictive value, and negative predictive value of 100, 96, 74, and 70 percent, respectively. In general, progression of such masses is very uncommon following chemotherapy [12], so we reserve surgery only for cases in which there is increased FDG activity. If none is seen, then males should undergo posttreatment surveillance. (See "Treatment of stage II seminoma" and "Posttreatment follow-up for testicular germ cell tumors", section on 'Seminoma'.)

On the other hand, the value of FDG-PET for surgical decision making in males with residual lesions ≥3 cm after chemotherapy was questioned in a study of 90 males without elevated tumor markers or nonseminomatous histology who had PET-positive residual lesions after chemotherapy [13]. The median diameter of the largest residual mass was 4.9 cm (range 1.1 to 14). Post-PET management included repeated imaging in 51 (57 percent), resection in 26 (29 percent), biopsy only in nine (10 percent), and RT in four (4 percent). Among the resected specimens, the histologic diagnosis was active seminoma in only five (19 percent); the remainder had necrosis only. No biopsy was positive for active seminoma. Disease progression occurred in 15 patients, including 11 of those managed with repeat imaging (22 percent), two patients despite, and two of the nine patients after a negative biopsy. All but one of the patients were successfully treated with salvage therapy.

Of the 51 patients managed with repeat imaging, 39 had a subsequent PET; in six, it became negative, and none of these patients relapsed. Of the 33 who had a positive PET on repeated imaging, resections were performed in six, only two of whom had residual seminoma. The remaining 27 were observed with repeated imaging, and seven (26 percent) eventually experienced relapse. Thus, despite a persistently positive PET, no relapse or active seminoma was detected in 24 of 33 patients (73 percent).

The positive predictive value of PET for the entire population was 23 percent, and none of the groups revealed meaningful improvement in positive predictive value, with values of 29 percent for definite PET positivity, 19 percent if the PET was performed later than six weeks after the end of chemotherapy, 32 percent in cases where the standardized uptake value was ≥4, and 22 percent if the residual mass was ≥3 cm.

Further validation of these findings is necessary before we change our recommendation to pursue surgery for residual masses >3 cm that are FDG avid. However, given the high false-positive rate of FDG-PET in this situation, we recommend obtaining a biopsy prior to pursuing surgery.

Nonseminomatous germ cell tumor — In contrast to seminoma, there is no role for FDG-PET scans in the work-up of residual disease seen on CT or MRI of males with NSGCT. A retroperitoneal lymph node dissection (RPLND) is indicated if there are one or more residual retroperitoneal lymph nodes larger than 1 cm present postchemotherapy on cross-sectional imaging.

Unlike in seminoma, imaging cannot reliably exclude the presence of active disease on the basis of size. For example, in one series of 87 patients [14]:

●Teratoma or viable malignant GCT was identified in 30 and 8 percent of males who had a residual retroperitoneal mass <2 cm, respectively.

●When the cut-off for residual mass size was reduced to <1 cm, 11 percent (6 of 54 males) had viable malignant GCTs. Despite this, the final pathology identified in subcentimeter disease does not appear to have any relevance to the prognosis of the patient. Therefore, surgical resection is not necessarily required in this specific subgroup of patients. (See 'Indications for surgical intervention' below.)

In contrast to the situation in seminoma, there is no role for FDG-PET scans in the work-up of residual disease seen on CT or MRI of males with NSGCT. PET is not sufficiently sensitive in detecting nodes that contain viable tumor [1,15], nor can it reliably differentiate teratoma from fibrosis. This was shown in a multicenter study of 121 males who underwent RPLND for residual masses greater than 1 cm after cisplatin-based chemotherapy [1]:

●PET scans were positive in only 47 of 67 cases (70 percent) with pathologically confirmed tumor.

●Among 54 cases that were pathologically negative, PET imaging was positive in 33.

DIFFERENTIAL DIAGNOSIS OF RESIDUAL MASSES — The differential diagnosis of residual masses present at the completion of chemotherapy includes [16-19]:

●Necrosis or fibrosis (40 to 50 percent of retroperitoneal masses).

●Mature or immature teratoma (30 to 40 percent).

●Residual non-teratomatous germ cell tumor (GCT) (10 to 20 percent), although the percentage of patients with viable GCT may be higher in those who have received multiple chemotherapy regimens [20,21].

Unfortunately, it is generally not possible to distinguish these possibilities on imaging. For example, multiple factors may predict the histology of residual retroperitoneal masses in males with nonseminomatous germ cell tumor (NSGCT), including the presence of teratomatous elements in the primary tumor, levels of serum tumor markers prior to chemotherapy, and the degree of reduction in mass size during chemotherapy [16-18,22-25]. However, none have sufficient accuracy to negate the role of surgery in identifying the final pathology [14,26,27].

RATIONALE FOR RESECTION OF RESIDUAL MASSES IN PATIENTS WITH NSGCT — The goal of resecting residual masses is to remove any residual teratoma or viable germ cell tumor (GCT). In addition, the presence of residual cancer is necessary in order to guide decisions about whether to administer additional chemotherapy.

There are multiple reasons to resect residual teratoma even though most teratomas behave in an indolent manner:

●Teratomas are relatively resistant to the chemotherapy and radiation therapy (RT) regimens for testicular GCTs because they are relatively slow growing tumors. Therefore, surgery is the only reliable way to eliminate them.

●Viable GCT may coexist with teratoma, which can lead to clinical recurrence if not resected [28,29].

●Malignant transformation of mature teratoma can occur [30]. Sarcomas or carcinomas arising from a teratoma are resistant to chemotherapy and are associated with a poor prognosis [30-32]. (See "Anatomy and pathology of testicular tumors", section on 'Teratoma'.)

●Indolent growth of a teratoma may compromise vital organ function and/or cause pain and other symptoms [33].

INDICATIONS FOR SURGICAL INTERVENTION — For males who are treated with primary chemotherapy or radiation therapy (RT) for advanced germ cell tumor (GCT), surgery may be indicated in males who exhibit either of the following scenarios:

Persistent elevation of the tumor markers following chemotherapy

●Nonseminomatous germ cell tumor (NSGCT) – In males with NSGCT, serum tumor markers that remain unchanged or sluggishly decline at the end of treatment without normalizing represent a cohort of males at high risk of relapse, with or without the presence of residual masses. Postchemotherapy resection of residual masses or retroperitoneal lymph node dissection (RPLND) is often followed by normalization of tumor markers and durable long-term survival [34-36]. As an example, of 114 patients with persistently elevated markers after first-line (n = 50) or second-line (n = 64) chemotherapy, postchemotherapy RPLND was associated with an overall five-year survival rate of 54 percent [36]. When stratified by final pathologic findings, the five-year survival rate for males with residual malignant GCT, teratoma, or fibrosis was 31, 78, and 86 percent, respectively.

●Seminoma – The only tumor marker of interest in males with a pure seminoma is the serum beta-human chorionic gonadotropin (beta-hCG); lactate dehydrogenase (LDH) is not sufficiently specific posttreatment to be of use, and by definition, these tumors do not produce alpha-fetoprotein (AFP). (See "Serum tumor markers in testicular germ cell tumors".)

For these males, persistently elevated or sluggishly declining serum beta-hCG is rare and the relevance of such a finding is not well defined. Therefore, decisions about management of residual masses in males with pure seminoma are not generally based on serum beta-hCG levels. The management of residual masses in males with pure seminomas is discussed below. (See 'Surgical approaches' below.)

Surveillance as an alternative option — It is important to note that there is no consensus on the best approach to manage males with NSGCTs who have persistently elevated serum tumor markers that are either stable or sluggishly declining at the end of treatment. For males who choose not to undergo surgery for whatever reason, surveillance is reasonable and may help determine the most appropriate management. The rationale for surveillance builds on the risk that tumor markers may rise in the immediate postoperative period while the patient is recovering from surgery, which may cause an undesirable delay to the start of second-line chemotherapy.

For males with NSGCT who choose not to proceed with surgery for whatever reason, we base subsequent decisions about surgery on the changes of tumor markers during surveillance:

●If the markers rise, patients have refractory GCT and should be treated with systemic chemotherapy. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)

●If the markers normalize over time, males should undergo resection of any residual mass >1 cm. While some experts perform a postchemotherapy RPLND in the absence of any residual mass (particularly in males who had retroperitoneal adenopathy present prior to treatment), this practice is controversial and we do not endorse it.

In the absence of rising markers or evidence of radiologic disease progression, there is no intervention required and males should continue on posttreatment surveillance. (See "Posttreatment follow-up for testicular germ cell tumors".)

Normalized tumor markers with abnormal imaging findings — For males who normalize their tumor markers but have abnormal imaging findings suggestive of persistent disease, the approach is based on the histologic type of GCT. This is discussed below.

Seminoma — In general, we do not resect or treat residual masses <3 cm in size following treatment for seminoma [12,37,38]. These masses rarely contain viable tumor if resected, and males rarely relapse if they are not resected. In addition, at least one report suggests that approximately one-half of such masses will disappear during surveillance within one year [39]. For males with larger lesions, we routinely will obtain a fluorodeoxyglucose (FDG) positron emission tomography (PET) scan to further assess whether or not to proceed with surgery. (See 'Imaging of residual disease' above.)

Nonseminomatous germ cell tumor — A residual mass is present in approximately 25 to 30 percent of males with NSGCT following chemotherapy. The majority of these are in the retroperitoneum, although such masses can occur at other sites, including the lung, mediastinum, liver, and brain. Rarely, the residual mass may be increasing in size despite normalized or decreasing tumor marker levels (the so-called "growing teratoma syndrome") [40-42].

For males with NSGCT, an RPLND is indicated if there are one or more residual retroperitoneal lymph nodes larger than 1 cm present postchemotherapy. Centers that are not accustomed to performing RPLNDs should refer the patient to a center of excellence with extensive experience in resecting postchemotherapy residual GCT masses whenever possible. Similarly, residual masses elsewhere, including enlarged lymph nodes in the thorax, neck, or pelvis, and metastatic lesions in the lung, liver, brain, or other organs should be resected if technically feasible. (See 'Surgical approaches' below.)

The approach to small lesions is controversial, and only low-quality data are available. Our approach is not to proceed with surgery in males with NSGCT with residual masses ≤1 cm if the tumor markers have normalized, despite the potential risk of GCT in these subcentimeter lesions. (See 'Nonseminomatous germ cell tumor' above.)

The rationale to proceed with surveillance rather than resection for these patients is based on single and multi-institutional observational studies that have consistently reported excellent outcomes without surgical intervention [14,26,43-45]. As an example, in one series of 161 patients with advanced NSGCT who had either a complete resolution of disease after chemotherapy (n = 115) or residual lesions ≤1 cm (n = 46), only 10 relapses were reported [44]. (See "Posttreatment follow-up for testicular germ cell tumors", section on 'NSGCT'.)

SURGICAL APPROACHES

Retroperitoneal lymph node dissection — The surgical technique and complications of retroperitoneal lymph node dissection (RPLND) are discussed separately. (See "Retroperitoneal lymph node dissection for early-stage testicular germ cell tumors", section on 'Surgical approaches' and "Retroperitoneal lymph node dissection for early-stage testicular germ cell tumors", section on 'Complications following RPLND'.)

The most common findings at RPLND include fibrosis/necrosis, teratoma, and viable germ cell tumor (GCT). As an example of contemporary experience, in a single-institution series of 504 patients who underwent RPLND, 51 percent of cases had fibrosis/necrosis, 37 percent had teratoma, and 15 percent had viable GCT [46]. Similar proportions have been seen in another series [47].

The outcomes in representative large series are illustrated by the following:

●Necrosis/fibrosis – The five-year disease-free and overall survival rates were 94 and 96 percent, respectively, in a series of 598 males in whom fibrosis/necrosis was identified at RPLND [48]. In the 36 patients who had a relapse, distant metastases were present in 27 (75 percent). Locoregional recurrence occurred in 14, including six with concurrent distant disease; only eight patients had locoregional disease alone at recurrence.

●Teratoma – Long-term follow-up in patients with residual teratoma at RPLND was analyzed in one institutional series of 210 cases [32]. Surgical findings included 178 with mature teratoma, 15 with immature teratoma, and 17 with teratoma with malignant transformation (85, 7, and 8 percent, respectively). The 10-year, disease-free survival after complete resection of residual teratoma was 80 percent. At a median follow-up of 37 months, 30 patients relapsed, including 10 with teratoma, five with teratoma with malignant transformation, and 15 with malignant GCT. Disease-specific survival at 5 and 10 years was 94 and 92 percent, respectively. On multivariate analysis, large size of the residual mass and intermediate or poor pretreatment International Germ Cell Cancer Collaborative Group (IGCCCG) risk status were predictors of a higher likelihood of recurrence (table 1). Similar results were seen in series from M. D. Anderson Cancer Center and Indiana University in patients who had teratoma identified at RPLND [49,50]. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Definition of risk'.)

●Viable germ cell tumor – In contrast to males with teratoma or necrosis/fibrosis discovered at postchemotherapy RPLND, males with viable malignant GCT have a relatively poor prognosis. This was illustrated by a series of 146 patients who had viable residual disease identified at posttreatment resection, all of whom had normal tumor markers prior to surgery [51]. The five-year, progression-free and overall survival rates were 64 and 73 percent, respectively. Adverse prognostic factors were incomplete resection of residual masses, more than 10 percent viable malignant cells in the resected residual mass, and an intermediate or poor IGCCCG prognostic classification at the start of first-line chemotherapy. A subsequent validation study testing these prognostic variables reported that overall survival rates in patients with zero, one, and two to three risk factors were 90, 86, and 52 percent, respectively [34].

Radical orchiectomy — For males who present with clinically advanced disease, a radical orchiectomy is performed to remove the primary tumor prior to chemotherapy whenever possible. Nonetheless, there are some males who present with life-threatening advanced disease who undergo systemic chemotherapy prior to orchiectomy. In this setting, orchiectomy of the testis that had the primary tumor should be performed upon completion of chemotherapy. (See "Radical inguinal orchiectomy for testicular germ cell tumors", section on 'Delayed orchiectomy'.)

Metastasectomy

Lung lesions — Males with persistent intrathoracic masses following cisplatin-based chemotherapy should undergo resection of disease if technically feasible. Prognosis following resection is favorable; over 80 percent can be expected to achieve long-term survival [52-54].

The outcomes of resection for postchemotherapy intrapulmonary residual masses were illustrated in a single-institution review of 251 males with testicular nonseminomatous germ cell tumor (NSGCT) [54]. The following findings were noted:

●Among males undergoing resection after their initial chemotherapy, the histopathology was teratoma, necrosis, persistent NSGCT, and non-germ cell cancer in 49, 32, 11, and 8 percent, respectively. In contrast, teratoma was less common and persistent NSGCT more common among those who underwent surgery after salvage chemotherapy (26 and 31 percent of cases, respectively).

●The majority of males with residual NSGCT after first-line chemotherapy were given additional chemotherapy. At long-term follow-up, 88 percent were alive and 79 percent continuously disease-free. The results were worse in patients resected after salvage chemotherapy. At long-term follow-up, 54 percent were alive and 44 percent continuously disease-free.

●There were only three postoperative deaths: one each from sepsis, pneumonia, and respiratory failure with pulmonary fibrosis.

Preoperative considerations — For patients with lung disease in whom pulmonary resection is planned, an ifosfamide-based regimen rather than a bleomycin-containing regimen may be a better option because ifosfamide is not associated with excess pulmonary toxicity. If bleomycin is administered, subsequent resection of residual intrathoracic disease may be accompanied by greater morbidity and mortality. The regimens used to treat males with metastatic GCT are reviewed separately. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)

The risks of pulmonary toxicity in patients who had received bleomycin are illustrated by a series of 530 males who presented for resection of residual intrathoracic disease following chemotherapy for either metastatic or primary mediastinal NSGCT [55]. In a subset of 32 males who required pneumonectomy or bilobectomy, the mean total dose of prior bleomycin was 360 units or milligrams, and the mean preoperative diffusing capacity was 66 percent of predicted. Prior treatment with bleomycin was associated with:

●Four operative deaths (13 percent) directly attributable to respiratory complications.

●Major pulmonary postoperative complications in an additional four males, including intubation for longer than 48 hours, a prolonged air leak with empyema, and need for supplemental oxygen at discharge.

●However, 14 of 20 long-term survivors had a satisfactory performance status at follow-up.

Further information on bleomycin-related lung toxicity is discussed separately. (See "Treatment-related toxicity in testicular germ cell tumors", section on 'Pulmonary' and "Bleomycin-induced lung injury".)

Mediastinal disease — In contrast to GCTs that are metastatic to the mediastinum, GCTs that arise in the mediastinum carry a very poor prognosis despite chemotherapy or a multimodality approach. (See "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum".)

Nonetheless, males with a mediastinal primary NSGCT who have one or more residual masses following chemotherapy are treated like other NSGCT patients with residual masses. For males with residual disease in both the retroperitoneum and mediastinum, we prefer a combined surgical approach with RPLND and mediastinal surgery [56,57]. In one report of 18 patients who underwent concomitant RPLND and mediastinal surgery, the overall five-year survival rate was 92 percent [57].

Neck disease — Although residual cervical nodal disease is an uncommon site of residual masses or late recurrence (<5 percent in one report [58]), such patients should be evaluated for modified neck dissection [59,60]. In one series of 45 such patients, only four recurred in the treated neck, and 97 percent of those with normal preoperative serum tumor markers remained disease-free.

Liver metastases — Resection of residual hepatic disease following chemotherapy can be performed safely and is as important as resection of residual retroperitoneal or pulmonary masses [61-65]. This was illustrated by a series of 52 patients with normal serum markers after chemotherapy [61]. After resection of residual hepatic disease, 35 (67 percent) were recurrence-free at last follow-up [61].

The decision to undertake hepatic resection should take into account the size of the hepatic lesions [64]. Lesions ≤10 mm in greatest dimension have a high probability of necrosis and can be closely monitored. In contrast, larger lesions have a higher risk of containing viable cancer and should be resected.

Brain metastases — Brain metastases may be present in males with testicular GCTs at the initial diagnosis, in conjunction with systemic relapse, or as an isolated relapse after control of systemic disease. Because brain metastases from GCTs are rare, there are insufficient data to make definitive treatment recommendations.

Almost all males receive cisplatin-based systemic chemotherapy as a component of their initial treatment for brain metastases because brain metastases generally occur in the setting of widely-metastatic disease. Following chemotherapy, local therapy in the form of either resection (where the disease is completely resectable) or radiation therapy (RT) is generally performed [66]. However, because the benefit of RT has not been clearly established, other experts favor chemotherapy (alone or combined with resection) [67]. For males presenting with multiple brain lesions, whole brain radiation is commonly given after chemotherapy, particularly for males who relapsed in the brain after first-line chemotherapy [66]. For males undergoing chemotherapy and RT, chemotherapy should be given first unless emergent local therapy is indicated. Administering chemotherapy and whole-brain RT at the same time may result in severe neurological toxicity [68]. As with other sites of disease, we favor surgical resection of all residual masses whenever possible in patients with NSGCTs.

The approach to patients with brain metastases is discussed separately. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Brain metastases'.)

Multisite disease — For males with residual retroperitoneal disease and disease at other sites, we suggest resection of retroperitoneal disease as the initial surgical treatment. Decisions about resection of other disease sites should be individualized based on patient and provider preferences.

For males who do undergo resection of retroperitoneal disease, we base subsequent decisions regarding the resection of residual disease on pathologic findings:

●If teratoma is found in the final pathology, further surgical resection is reasonable.

●If viable GCT is found, patients have chemorefractory disease. Therefore, patients should be counseled about the role of further chemotherapy (with or without further disease resection), preferably in the context of a specialty multidisciplinary discussion. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors".)

For males with multiple residual masses following cisplatin-based chemotherapy, up to 33 percent can have a complete response following resection of disease [69]. However, 50 percent of those that undergo surgery once tumor markers have normalized will have evidence only of necrosis at final pathology and will have undertaken surgery unnecessarily [69-72]. In one of the largest series, 159 males underwent simultaneous RPLND and thoracotomy following cisplatin-based chemotherapy [71]. The finding of necrosis in the retroperitoneal specimen was associated with an 89 percent probability of necrosis in the lung.

Despite these data, others report discordant histologies in up to 50 percent of males undergoing resections at different anatomic sites and advocate the need for resection of all areas of residual disease [73-75].

ROLE OF ADJUVANT CHEMOTHERAPY — Following resection of residual masses that contain viable germ cell tumors (GCTs), at least two further cycles of chemotherapy are advised, although retrospective studies have reported conflicting results with regard to whether such chemotherapy is associated with improved outcomes [34,51].

Successful outcomes have been reported in males who refuse further chemotherapy following surgery alone, even if tumor markers are elevated preoperatively, although this is not the preferred approach [76]. However, it may be possible to identify patients for whom the prognosis is favorable enough to forego chemotherapy. Among patients with viable tumor at resection following chemotherapy, factors associated with a favorable outcome include [34,51,77]:

●Complete resection

●Less than 10 percent viable tumor cells on final pathology

●Good risk disease according to the International Germ Cell Consensus Classification (for males who presented with advanced disease)

Males who meet all these criteria have been reported to have a 90 and 92 percent five-year overall and progression-free survival rate, respectively.

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

●Importance of surgery – Although testicular germ cell tumors (GCTs) are highly chemosensitive, surgical management is an important component of multimodality treatment for males with advanced disease. (See 'Introduction' above.)

●Differential diagnosis of residual masses – Residual masses present following chemotherapy can be due to necrosis/fibrosis, teratoma, or viable residual GCT, and it is generally not possible to distinguish these possibilities without a tissue diagnosis. (See 'Differential diagnosis of residual masses' above.)

●Nonseminomatous germ cell tumors

•Normal serum tumor markers – For patients with nonseminomatous GCTs and normal serum tumor markers, we suggest surgery to resect all residual masses >1 cm throughout the body (Grade 2C). For patients with smaller lesions (ie, <1 cm), careful surveillance is preferred, but retroperitoneal lymph node dissection (RPLND) is a reasonable alternative for males with subcentimeter residual retroperitoneal masses. (See 'Nonseminomatous germ cell tumor' above.)

•Stable or elevated tumor markers – Patients with nonseminomatous GCTs and stable or persistently elevated serum tumor markers should undergo either close surveillance or resection of all residual masses. In the absence of a clear survival benefit to surgery, either approach is reasonable. For patients who opt for surveillance in the presence of slowly declining markers, we suggest surgery once their markers normalize (Grade 2C). (See 'Persistent elevation of the tumor markers following chemotherapy' above.)

●Seminoma – For males with seminoma, our approach takes into account the size of the lesion (see 'Seminoma' above):

•For males with residual masses <3 cm as detected on cross-sectional imaging, we suggest surveillance rather than surgery (Grade 2C).

•If a residual mass ≥3 cm is identified, we suggest a positron emission tomography (PET) scan for further clarification, rather than immediate surgery (Grade 2C). If the PET scan is positive, we suggest surgery (Grade 2C). If the PET scan is negative, we suggest surveillance (Grade 2C).

●Retroperitoneal lymph node dissection – RPLND is an important component of a multidisciplinary approach in these patients, but surgery demands a high level of expertise with respect to both the surgery itself and postoperative care. Thus, these males should be managed in centers of excellence where a high volume of testicular cancer patients is seen. (See 'Retroperitoneal lymph node dissection' above.)

●Supradiaphragmatic disease without retroperitoneal involvement – We suggest surgical resection rather than observation for patients who have residual lesions at supradiaphragmatic sites but no involvement of the retroperitoneum (Grade 2C). The most common sites of such involvement include the lungs and mediastinum; neck involvement is less common. (See 'Metastasectomy' above.)

●Liver metastases – For patients with residual lesions in the liver following chemotherapy, we suggest resection of lesions that are greater than 10 mm in greatest diameter (Grade 2C). Smaller lesions can be carefully observed, with resection if there is any evidence of growth. (See 'Liver metastases' above.)

●Brain metastases – Patients with brain metastases generally are managed with cisplatin-based chemotherapy followed by resection of residual masses when feasible. The role of whole-brain radiation is controversial, but it is an option for patients with unresectable residual masses that cannot be treated with stereotactic radiosurgery. (See 'Brain metastases' above and "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Brain metastases'.)

●Supradiaphragmatic and retroperitoneal disease – For males with residual lesions at both supradiaphragmatic and retroperitoneal sites, we suggest a bilateral RPLND as the initial intervention (Grade 2C). Further treatment should be based on the histopathological results (see 'Multisite disease' above):

•For males with residual teratoma, we suggest resection of all other sites of disease (Grade 2C).

•For males with viable GCT, we suggest postoperative chemotherapy (Grade 2C).

•For males with only necrosis and fibrosis identified with no viable tumor seen, we suggest surveillance rather than further resection of residual lesions (Grade 2C).

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Timothy D Gilligan, MD, who contributed to earlier versions of this topic review.