This is an original JCO publication from 2010. Please visit the JCO website to access the full article.
Uses of Serum Tumor Markers in Adult Males with Germ Cell Tumors
Timothy D. Gilligan, Jerome Seidenfeld, Ethan M. Basch, Lawrence H. Einhorn, Timothy Fancher, David C. Smith, Andrew J. Stephenson, David J. Vaughn, Roxanne Cosby and Daniel F. Hayes
|1. Screening||Asymptomatic adults||Recommendation 1. The Panel recommends against use of STMs or any other blood tests to screen for GCTs.|
|2. Diagnosis||A. To determine need for orchiectomy||Recommendation 2A. The Panel recommends drawing blood to measure serum AFP and hCG before orchiectomy for all patients suspected of having a testicular GCT to help establish the diagnosis and interpret postorchiectomy levels. However, the Panel recommends against use of STM assay results to guide decision making on need for an orchiectomy. Concentrations in the normal range do not rule out testicular neoplasm or the need for diagnostic orchiectomy.|
|B. To evaluate CUP possibly derived from GCT||Recommendation 2B. The Panel recommends against using serum AFP and hCG assay results to guide treatment of patients with CUP and indeterminate histology, because evidence is lacking to support this use. Consider treatment with a chemotherapy regimen for disseminated GCT in patients presenting with undifferentiated midline carcinoma even if serum hCG and AFP concentrations are within normal ranges.|
|C. To evaluate patients presenting with metastasis and a primary tumor in testis, retroperitoneum, or anterior mediastinum||Recommendation 2C. In rare male patients presenting with testicular, retroperitoneal, or anterior mediastinal primary tumor and whose disease burden has resulted in an urgent need to start treatment, substantially elevated serum AFP and/or hCG may be considered sufficient for diagnosis of GCT. For such rare, medically unstable patients, treatment need not be delayed until after tissue diagnosis.|
|Part I: NSGCT|
|I-3. Monitoring during treatment (or observation)||A. For staging and prognosis before chemotherapy and/or additional surgery||Recommendation I-3A-1. Although evidence is lacking to determine whether decisions based on STM assay results improve survival or other health outcomes for these patients, the Panel recommends measuring serum AFP, hCG, and LDH for all patients with testicular NSGCT shortly after orchiectomy and before any subsequent treatment. The magnitude of postorchiectomy STM elevations is used to stratify risk and select treatment but must be interpreted appropriately. Serial STM measurements may be needed to determine whether STM levels are rising or falling and, if falling, whether the decline approximates the marker's biologic half-life.|
|Recommendation I-3A-2. Although direct evidence is lacking to demonstrate that decisions based on STM assay results improve survival or other health outcomes for these patients when compared with decisions made without assay results, the Panel recommends measuring serum AFP, hCG, and LDH before chemotherapy begins for those with mediastinal or retroperitoneal NSGCTs to stratify risk and select treatment.|
|B. To predict response to or benefit from treatment||Recommendation I-3B-1. The Panel recommends measuring AFP and hCG shortly before RPLND in patients with clinical stage I or II NSGCT; those with rising concentrations are beyond stages IA or IB and need systemic therapy similar to the regimens used for patients with stage III disease.|
|Recommendation I-3B-2. Although direct evidence is lacking to determine whether decisions based on STM assay results improve survival or other health outcomes when compared with decisions made without assay results, the Panel recommends measuring hCG, AFP, and LDH immediately prior to chemotherapy for stage II/III testicular NSGCT. The magnitude of marker elevations guides chemotherapy regimen choice and treatment duration.|
|C. To monitor response or progression during or soon after therapy||Recommendation I-3C. Although direct evidence is lacking to determine whether monitoring treatment response with STM assays during chemotherapy improves survival or other health outcomes of patients with NSGCT, the Panel recommends measuring serum AFP and hCG at the start of each chemotherapy cycle and again when chemotherapy concludes. However, the Panel sees no indication to delay the start of chemotherapy until after results of STM assays are known. Rising AFP and/or hCG levels during chemotherapy usually imply progressive disease and the need to change regimen. However, tumor lysis from chemotherapy, particularly during the first cycle, may result in a transient spike in STM levels, and such a spike does not represent treatment failure. Resect all residual disease for patients whose STM levels have normalized and who have resectable residual mass(es) following chemotherapy. Slow decline during treatment conveys higher risk of treatment failure but does not indicate need to change therapy. Persistently elevated but slowly declining postchemotherapy levels do not indicate immediate need for additional chemotherapy; resection of residual masses need not be delayed until STM levels normalize.|
|I-4. For surveillance||After presumably definitive therapy||Recommendation I-4. Although direct evidence is unavailable to determine whether monitoring STM concentrations during surveillance and following definitive therapy for NSGCT improves patients' survival or other health outcomes, the Panel recommends measuring AFP and hCG at each visit during surveillance after definitive therapy for NSGCT, regardless of stage. Since evidence also is lacking to directly compare outcomes for different monitoring intervals or durations, the Panel recommends using intervals within the range used by the available uncontrolled series: every 1 to 2 months in the first year, every 2 to 4 months in the second year, every 3 to 6 months in the third and fourth years, every 6 months in the fifth year, and annually thereafter. The Panel also recommends that surveillance should continue for at least 10 years after therapy is completed.|
|Part II. Seminoma|
|II-3. Monitoring during treatment (or observation)||A. For staging and prognosis before RPLND, radiation, or chemotherapy||Recommendation II-3A. Although direct evidence is lacking to determine whether measuring STM concentrations improves survival or other health outcomes of these patients, the Panel recommends measuring postorchiectomy serum concentrations of hCG and/or LDH for patients with testicular pure seminoma and preorchiectomy elevations. However, the Panel recommends against using postorchiectomy serum concentrations of either hCG or LDH to stage or predict prognosis of patients with involved nodes and/or metastasis.|
|B. To predict response to or benefit from treatment||Recommendation II-3B. The panel recommends against using tumor marker levels to guide treatment decisions for seminoma. Evidence is lacking that selecting therapy based on tumor marker levels yields better outcomes.|
|C. To monitor response or progression during or soon after therapy||Recommendation II-3C. The Panel recommends against using tumor markers to monitor response or progression of seminomas during treatment. However, serum hCG and AFP should be measured when seminoma treatment concludes. Rising concentrations usually indicate progressive disease and the need for salvage therapy (usually chemotherapy).|
|II-4. For surveillance||After presumably definitive therapy||Recommendation II-4. Conclusive evidence is lacking for clinical utility of STMs in post-treatment surveillance for stage I seminoma, and the Panel recommends against this use. However, while direct evidence is unavailable to determine whether monitoring STM concentrations improves survival or other health outcomes of patients who have completed therapy for advanced seminoma, rising levels may be the earliest sign of relapse, and the Panel recommends measuring STMs at each visit for these patients. Since evidence also is lacking to directly compare outcomes for different monitoring intervals or durations, the Panel recommends using intervals within the range used in the available uncontrolled series: every 2 to 4 months in the first year, every 3 to 4 months in the second year, every 4 to 6 months in the third and fourth years, and annually thereafter. The Panel also recommends that surveillance should continue for at least 10 years after therapy is completed.|
Abbreviations: STM, serum tumor marker; GCT, germ cell tumor; AFP, α-fetoprotein; hCG, human chorionic gonadotropin; CUP, cancers of unknown primary; NSGCT, nonseminomatous germ cell tumor; LDH, lactate dehydrogenase; RPLND, retroperitoneal lymph node dissection.
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