INTRODUCTION — Testicular germ cell tumors (GCTs) are one of the most curable solid neoplasms due to improved staging and surgical techniques, the use of platinum-based combination chemotherapy, and the availability of serum tumor markers (beta subunit of human chorionic gonadotropin [beta-hCG], alpha fetoprotein [AFP], and lactate dehydrogenase [LDH]) to monitor for the response to treatment and the presence of occult disease. For men with testicular GCTs, the five-year survival rate is over 95 percent. (See "Overview of the treatment of testicular germ cell tumors" and "Serum tumor markers in testicular germ cell tumors".)
The follow-up and surveillance for recurrence in men who have completed their initial definitive treatment for testicular cancer will be reviewed here. The use of serum tumor markers during the initial treatment of testicular GCTs is discussed separately.
●(See "Serum tumor markers in testicular germ cell tumors", section on 'Monitoring response to therapy'.)
●(See "Active surveillance following orchiectomy for stage I testicular germ cell tumors".)
ONCOLOGIC FOLLOW-UP — At the conclusion of treatment, surveillance is appropriate for:
●Men with low-risk stage I testicular GCTs treated with orchiectomy alone. (See "Active surveillance following orchiectomy for stage I testicular germ cell tumors".)
●Men with a complete response, defined as normal posttreatment serum tumor markers (alpha fetoprotein [AFP], beta-human chorionic gonadotropin [beta-hCG], and/or lactate dehydrogenase [LDH]) and no evidence of disease on imaging studies.
●Men with a partial response, defined as stable or declining tumor markers (without normalization). This may be associated with evidence of persistent disease on imaging.
Routine follow-up care for men who have successfully completed therapy for testicular cancer consists of periodic history and physical examinations (including testicular examination), assessment of serum tumor markers (beta-hCG, AFP, and/or LDH), and radiographic studies.
Factors that influence the nature and intensity of follow-up after completion of initial definitive therapy include histology (seminoma versus nonseminomatous germ cell tumors [NSGCTs]), risk of recurrence, and treatment (particularly the use of surgery or radiation therapy to treat the retroperitoneal lymph nodes).
Men who have rising tumor markers and/or radiographically documented progressive disease following treatment should be evaluated for recurrent disease. (See 'Detection of recurrent disease' below.)
Duration of follow-up after treatment — The intensity of follow-up is guided in part by the probability of relapse over time.
●For men with seminoma, the median time to relapse is 14 months, but up to one-third of relapses occur more than three years after completion of treatment [1].
●For men with NSGCT, over 95 percent of relapses occur within the first two years following orchiectomy [1].
Although most relapses occur within the first five years for both seminoma and NSGCT, late recurrences are rare but can occur [2-4]. In one study that evaluated 1949 patients, 10 of 1123 men with seminoma (0.8 percent) and 15 of 826 men with NSGCT (1.8 percent) recurred more than five years after the original diagnosis [2]. Other series have reported a higher incidence of late recurrences [5,6], but these may be subject to referral bias.
Therefore, follow-up is most intensive during the first one to two years after treatment and then gradually decreases. However, most groups now recommend that follow-up continue for at least 10 years following initial treatment because of the risk of late relapse. The treatment of relapsed testicular GCTs is discussed elsewhere. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors".)
Monitoring approaches — The basic approaches used to monitor a man following definitive therapy for a testicular GCT include:
●History and physical examination (see 'History and physical examination' below)
●Serum tumor markers (see 'Serum tumor markers' below)
●Imaging of the chest, abdomen, and pelvis (see 'Radiographic studies' below)
There are no prospective randomized trials that have defined the optimal follow-up strategy for men who have completed their initial treatment. (See 'Guidelines for follow-up' below.)
History and physical examination — Posttreatment history and physical examination should be performed on the same schedule as measurement of tumor markers. Close attention should be paid to cervical and supraclavicular nodal regions, the abdominal exam (for the presence of masses or hepatomegaly), and the presence of neurologic signs or symptoms. (See 'Guidelines for follow-up' below.)
Testicular examination should be performed at each visit because of the higher incidence of contralateral testis cancer in men with unilateral GCTs and of testis cancers in men with primary extragonadal GCTs. (See "Epidemiology of and risk factors for testicular germ cell tumors" and "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum" and "Approach to the care of long-term testicular cancer survivors", section on 'Contralateral testicular cancer'.)
Serum tumor markers — For men who have completed definitive therapy, tumor markers (beta-hCG, AFP, and LDH) should be measured at the same frequency as the history and physical exam. Of these, AFP is the most sensitive to detect relapsed disease, while LDH is the least sensitive and least specific [7].
For men with NSGCTs, serum concentrations of beta-hCG and/or AFP are elevated in 85 percent of patients at diagnosis. Following treatment, periodic measurements of serum beta-hCG and AFP represent the most sensitive means of detecting early relapse. (See 'NSGCT' below.)
For men with seminoma, we generally monitor serum tumor markers, although relapse is almost always detected by exam or by imaging [7,8]. Beta-hCG is increased in 15 to 20 percent of those with advanced disease. However, AFP, by definition, is never elevated in patients with pure seminoma [9]. Although LDH is a less sensitive and less specific tumor marker than either beta-hCG or AFP, it may be the only elevated marker in some men with seminoma. (See 'Seminoma' below and "Serum tumor markers in testicular germ cell tumors", section on 'Human chorionic gonadotropin' and "Serum tumor markers in testicular germ cell tumors", section on 'Alpha-fetoprotein'.)
Radiographic studies — Chest radiographs can be performed with the same frequency as tumor markers as a component of the posttreatment surveillance schedule. Either computed tomography (CT) or magnetic resonance imaging (MRI) scans are used to monitor for disease recurrence in the abdomen or pelvis. However, there are no firm data supporting the benefit of these studies. (See 'Guidelines for follow-up' below.)
●In one series, 290 men with disseminated testicular cancer were followed on a posttreatment surveillance protocol that included serum tumor markers, physical examination, and chest radiographs after attaining a complete remission from chemotherapy [10]. Tumor relapse was documented in 33 (11.4 percent). Relapse was detected by rising tumor markers only in 27 (82 percent) and by rising tumors markers plus abnormal physical examination in four men. A total of 10,160 routine chest radiographs were performed during surveillance, and none played a role in detecting tumor relapse. Prior to the initiation of treatment for relapsed disease, all patients but one had elevated serum tumor markers.
●The utility of periodic CT scans of the abdomen and pelvis was evaluated in a series of 170 men undergoing surveillance following orchiectomy for stage I NSGCTs [11]. History and physical examination, serum tumor markers, CT of the abdomen and pelvis, and chest radiography provided the initial evidence of progression in 38, 71, 71, and 8 percent of patients, respectively. Removal of routine chest radiography from the surveillance protocol would not have altered the detection of progressive disease.
There are real concerns about the risk of second malignancies due to the radiation from CT scans. Efforts to reduce the amount of radiation by using different techniques, such as MRI, or changing the number and/or frequency of CT scans remain an area of active investigation. (See "Radiation-related risks of imaging".)
Guidelines for follow-up — There are no prospective randomized trials that define the optimal follow-up strategy for men who have completed their initial treatment. Multiple urologic and oncologic groups have published guidelines or recommendations based upon histology (NSGCTs versus seminomas) and stage of disease using data from observational studies [9,12-19]. Although there are some differences in guidelines between these groups, all rely upon interval history and physical examination, assessment of serum tumor markers, chest radiographs to assess pulmonary disease, and CT or MRI to assess the abdomen and pelvis.
Our approach is consistent with follow-up guidelines from the National Comprehensive Cancer Network (NCCN) [19]:
NSGCT
●Active surveillance after inguinal orchiectomy for clinical stage I disease — A history and physical examination, and serum tumor markers (AFP, beta-hCG, and LDH) should be obtained every two months for the first year, every three months during the second year, every four to six months in year 3, then decreasing to annually beginning year 5. CT of the abdomen and pelvis should be obtained every four to six months in year 1, gradually decreasing to annually in year 3 or 4. Chest radiograph monitoring is indicated at 4 and 12 months for patients with clinical stage IA disease, and then annually thereafter. For those with stage IB disease, chest radiograph should be monitored every two months during the first year and then gradually decrease to annually beginning year 5. Because of the amount of radiation from CT scans in young, otherwise healthy patients, methods to reduce radiation, such as low radiation dosage protocols or MRI studies, are being evaluated. (See "Active surveillance following orchiectomy for stage I testicular germ cell tumors".)
●Clinical stage IB treated with adjuvant chemotherapy — A history and physical examination, and tumor markers should be obtained every three months for years 1 and 2, every six months in years 3 and 4, and then annually. CT of the abdomen and pelvis should be performed annually the first two years and repeated only if clinically indicated thereafter. Chest radiograph is recommended every 6 to 12 months for the first year, annually for year 2, and then as clinically indicated.
●Pathologic stage II treated with retroperitoneal lymph node dissection (RPLND) without adjuvant chemotherapy — A history and physical examination, a chest radiograph, and tumor markers should be obtained every two to three months for years 1 and 2, gradually decreasing to every six months in year 4, and then once a year starting in year 6. CT of the abdomen and pelvis should be performed at three to four months and repeated only if clinically indicated thereafter.
●Pathologic stage II managed with RPLND and adjuvant chemotherapy — A history and physical examination, a chest radiograph, and tumor markers should be obtained every six months for the first two years and annually thereafter. CT of the abdomen and pelvis should be obtained after RPLND and as clinically indicated thereafter.
●Clinical stage II/III managed with chemotherapy with or without RPLND following chemotherapy — A history and physical examination, and tumor markers should be obtained every two months during the first year, every three months during the second year, and every six months for years 3 through 5. Chest radiograph is indicated every six months for the first two years, annually during years 3 and 4, and then as clinically indicated. Abdominal and pelvic CT is indicated every six months during the first year, every 6 to 12 months during year 2, annually for year 3, and then as clinically indicated.
Seminoma
●Stage I disease
•Men undergoing active surveillance after inguinal orchiectomy – A history and physical exam, and tumor markers (AFP, beta-hCG, and LDH) should be obtained every three to six months for the first year, every 6 to 12 months in years 2 and 3, and then annually. CT of the abdomen and pelvis should be obtained at 3, 6, and 12 months, every 6 to 12 months in years 2 and 3, and then every 12 to 24 months in years 4 and 5. A chest radiograph is performed only if clinically indicated. (See "Active surveillance following orchiectomy for stage I testicular germ cell tumors".)
•Men treated with adjuvant therapy (chemotherapy or radiation therapy) – A history and physical exam, and tumor markers (AFP, beta-hCG, and LDH) should be obtained every 6 to 12 months for years 1 and 2, and annually thereafter. CT of the abdomen and pelvis should be performed annually for years 1 to 3 and then as clinically indicated thereafter. A chest radiograph should be performed only if clinically indicated.
●Stage II-III disease
•Men treated with radiation therapy to the ipsilateral iliac and paraaortic nodes – A history and physical exam, and tumor markers (AFP, beta-hCG, and LDH) should be obtained every three months for year 1, then every six months until year 5. CT of the abdomen and pelvis should be performed at three months and between 6 to 12 months during year 1, then annually during years 2 and 3, and subsequently as clinically indicated. Chest radiograph should be obtained every six months for years 1 and 2.
•Men treated with combination chemotherapy — A history and physical exam, chest radiograph, and tumor markers (AFP, beta-hCG, and LDH) should be obtained every two months for year 1, gradually decreasing to every six months in year 3, then annually starting year 5. For men treated with RPLND post-chemotherapy, a CT of the abdomen and pelvis should be performed three to six months after surgery and subsequently as clinically indicated. Chest radiograph should be performed every two months during the first year, every three months during the second year, and annually thereafter.
Detection of recurrent disease — Rising tumor markers and/or the presence of radiographically documented progressive disease are usually an indication of disease recurrence or progression. Men who exhibit either of these during surveillance are candidates for further treatment. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors".)
Interpreting serum tumor markers — Serum tumor markers are rarely a sign of recurrence among men with seminoma [7,8]. However, our approach to interpreting serum tumor markers depends on the scenario:
●For men who experienced declining serum tumor markers during treatment but did not normalize by the end of treatment, we consider an increase in AFP or beta-hCG a sign of disease recurrence. However, no particular level of increase is pathognomonic of a tumor recurrence.
●For men who normalized serum tumor markers, we do not consider values that fluctuate (or increase) but stay within the normal range a sign of relapse.
●For men with a stable but elevated level of AFP (ie, AFP level 25 percent higher than the upper limit of normal), we consider an increase in the AFP or beta-hCG a sign of disease recurrence.
Pulmonary nodules — Men who received bleomycin as part of their original treatment are at risk for pulmonary toxicity during follow-up. This may present on imaging (chest radiograph or CT) as nodular lesions shortly after the completion of chemotherapy (table 1) [20]. Characteristically, these are subpleural in location, and serum tumor markers are normal. (See "Bleomycin-induced lung injury" and "Approach to the care of long-term testicular cancer survivors", section on 'Bleomycin-induced lung injury'.)
Growing teratoma syndrome — Benign teratomatous elements may enlarge during or after chemotherapy, mimicking progressive or relapsed disease [21]. In such patients, tumor markers may be normal. Complete surgical resection is indicated rather than additional chemotherapy. (See "Approach to surgery following chemotherapy for advanced testicular germ cell tumors", section on 'Rationale for resection of residual masses in patients with NSGCT'.)
False-positive elevation of serum beta-hCG — Because there is some cross reactivity with luteinizing hormone (LH), a false-positive elevation of serum beta-hCG may occur in men with hypogonadism, which may occur following systemic chemotherapy. Administration of testosterone may resolve this issue. (See "Serum tumor markers in testicular germ cell tumors" and "Clinical features and diagnosis of male hypogonadism" and "Causes of secondary hypogonadism in males" and "Approach to the care of long-term testicular cancer survivors", section on 'Hypogonadism'.)
TREATMENT-RELATED COMPLICATIONS — Men who have been treated for a testicular GCT are at risk for late complications of therapy, as well as for recurrence of cancer. The immediate and late complications of treatment in men with testicular GCTs are discussed in detail elsewhere. (See "Treatment-related toxicity in men with testicular germ cell tumors" and "Approach to the care of long-term testicular cancer survivors".)
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 — Testicular germ cell tumors (GCTs) are one of the most curable solid neoplasms due to advances in treatment, including cisplatin-based chemotherapy and the use of serum tumor markers to monitor response to treatment and to detect minimal residual disease. Aggressive treatment of relapsed disease is required to maintain the high cure rate while minimizing the toxicity associated with treatment. (See "Overview of the treatment of testicular germ cell tumors" and "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors".)
●Most patients who will relapse do so within the first one to two years after their initial treatment. Late relapses (after five years) can occur but are rare. The intensity of follow-up is dictated by the histology of the original tumor (seminoma versus nonseminomatous GCT), and the stage and risk of recurrence at original presentation.
●Oncologic follow-up after initial therapy includes history and physical examination, monitoring serum tumor markers (beta-human chorionic gonadotropin [beta-hCG], alpha-fetoprotein [AFP]) for evidence of recurrence, and imaging studies (chest radiograph, magnetic resonance imaging [MRI] or computed tomography [CT] of abdomen and pelvis). The optimal schedules for follow-up have not been defined in clinical trials, but empiric guidelines have been established based upon observational experience. (See 'Guidelines for follow-up' above.)
●Several clinical situations may mimic tumor relapse and must be carefully distinguished from a true relapse to prevent overtreatment. These include pulmonary nodules secondary to bleomycin lung injury, the growing teratoma syndrome, and false-positive elevation of beta-hCG that is due to hypogonadism. (See 'Detection of recurrent disease' above.)
●In addition to oncologic follow-up, men successfully treated for testicular GCTs require surveillance for complications of treatment. (See "Treatment-related toxicity in men with testicular germ cell tumors" and "Approach to the care of long-term testicular cancer survivors".)
ACKNOWLEDGEMENT — The UpToDate editorial staff acknowledges William K Oh, MD, who contributed to earlier versions of this topic review.
