Cellular localization of alpha-fetoprotein and human chorionic gonadotropin in germ cell tumors of the testis using and indirect immunoperoxidase technique.

An immunohistologic study of 21 patients with germ cell tumors of the testis with measured serum levels of chorionic gonadotropin (HCG) and alpha-feto protein (AFP) was undertaken to correlate the various types of neoplasms with the presence of these tumor markers in the tissue and serum. AFP was demonstrated in mononuclear embryonal cells within embryonal carcinoma and endodermal sinus tumor. HCG was identified within syncytiotrophoblastic giant cells, frequently in association with embryonal carcinoma, and rarely with endodermal sinus tumor and seminoma, as well as in the syncytiotropho-blastic component of choriocarcinoma. Eighteen of the 21 patients (86%) had elevated tumor markers in their serum; serum HCG alone was elevated in five (24%), AFP alone in five (24%) and both were elevated in eight (38%). There was tissue localization of HCG in 12 of the 13 patients (92%) with elevated serum HCG while AFP was identified in the tumor in eight of the 13 patients (53%) with elevated serum AFP levels. Based on these findings, a tentative immunohistologic classification of germ cell tumors utilizing AFP and HCG is proposed. Thus, embryonal carcinoma, adult type, is frequently associated with both AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma and teratoma are unlikely to be associated with either marker.     

Lactic dehydrogenase in the monitoring and prognosis of testicular cancer

In a prospective study of 80 patients with germinal testicular cancer, serial determinations of lactic dehydrogenase (LDH), alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) were followed for a mean of 18.1 months. Serum LDH was found to be elevated more frequently with increasing tumor bulk. LDH was elevated in 78.0% of the patients with Stage III disease but only 26.3% of the Stage II patients and 20.0% of the pre-orchiectomy Stage I patients. In this study, serum HCG and AFP levels were always elevated in the presence of elevated serum LDH levels except in one patient when LDH was the only elevated marker, in which case it correlated with clinical disease. Correlation of these three serum markers is shown by elevation of LDH in 78.0% of the Stage III patients, AFP in 78.6%, and HCG in 76.2%. In addition, of the 43 patients who had normal LDH levels on initial presentation, their mean survival time (MST) at the end of the study was 15.5 months while the 26 patients who had elevated LDH levels on initial presentation had an MST of 9.2 months. Serum LDH, therefore, may be useful in evaluating patient prognosis as well as an adjunct in monitoring the treatment of patients with bulky testicular cancer. The combination of LDH and HCG has been utilized to monitor the treatment of seminoma.     

Serum neuron-specific enolase. A marker for responses to therapy in seminoma

Neuron-specific enolase (NSE) was evaluated as a serum marker in 105 patients with testicular cancer and compared with the established tumor markers alphafetoprotein (AFP) and human chorionic gonadotropin (HCG). Increased serum NSE activity was measured in eight of 11 (73%) patients with metastatic seminoma. Serum NSE concentrations fell to within the normal range following chemotherapy. Localization of NSE in seminoma cells was demonstrated immunohistochemically. Only six of 40 (15%) patients with metastatic nonseminomatous germ cell tumors showed elevated serum NSE levels. AFP and HCG were both positive in 70% of patients in this group, and NSE determination gave no additional information. Serum NSE concentrations were normal in 53 of 54 testicular cancer patients after orchiectomy and there was no evidence of metastatic disease; only one had borderline NSE levels, indicating the specificity of serum NSE determination. NSE is a new marker of seminoma and its measurement may be of clinical value in monitoring chemotherapy in patients with metastatic seminoma.     

Human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) in sera and tumor cells of patients with testicular seminoma: a prospective study.

The HCG and AFP have been quantitated in the sera of 130 patients with the diagnosis of testicular seminoma utilizing a specific double antibody radioimmunoassay. These tumor markers also were localized in tumor cells of some of these patients utilizing an indirect immunoperoxidase technique. 11 of 130 patients had elevated serum levels of HCG. The HCG molecules have been localized in the syncytiotrophoblastic giant cell (STGC) that is occasionally observed in seminomas. None of the patients with pure seminoma had an elevated level of serum AFP. We have concluded that in patients with pure seminoma the level of serum HCG can be elevated (10 of 130 or 7.6%), but we have not observed elevated serum levels of AFP in these patients.     

Multiple antigens as marker substances in germinal tumors of the testis.

Germinal cell tumors of the testis were studied for the presence of several tumor-associated antigens. Antisera were produced by immunizing rabbits with the purified antigens of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and hepatoma ferritin. Indirect immunofluorescence on embryonal carcinoma with or without teratoma components demonstrated that their staining range was 1--60 per cent with antiserum against AFP, 0--16 per cent with anti-serum against ferritin, and 0-40% with antiserum against CEA. Ferritin-like substances have not been described previously in germinal tumors of the testis. No staining was seen with seminoma cells or benign testicular tissues. Raised serum levels of AFP and the ferritin-like substance were related both to the presence of tumor and to dissemination of the disease. CEA occurred transiently in serum. Eleven patients with primary tumors had no antigen in their sera and have all survived, but the median survival time for 8 patients with either antigen in preoperative sera was 12 months. Five patients with advanced tumor in whom neither AFP nor ferritin was detected had a much longer median survival time (58 mo) than did 13 patients with high levels of serum AFP or ferritin (12 mo). The presence of either AFP or ferritin in sera of patients with primary or advanced disease, therefore, seemed to indicate a poor prognosis. The determination of both substances in serum may be useful in the follow-up of patients with certain types of testicular tumors. The proportion of cells containing each antigen varied in the different tumors. Similarly, each antigen could occur independently in serum. This suggested that certain germ cell tumors contained subpopulations of cells, which differed in their production and release of the antigens studied.     

Neuron-specific enolase--a serum tumour marker in seminoma?

The clinical significance of neuron-specific enolase (NSE) as a tumour marker was evaluated in 54 patients with seminoma. Before orchiectomy NSE was elevated in six out of 21 patients with stage I seminoma and 11 out of 16 patients with metastases. After orchiectomy NSE normalised in all evaluated stage I cases, but was still elevated in six out of 12 patients with metastatic disease. NSE monitored the effect of cisplatin-based chemotherapy in patients with metastases. In some patients, increased serum NSE was found together with raised levels of human choriogonadotropin (HCG) and lactate dehydrogenase (LDH), while in others only NSE was elevated. No false positive NSE values were observed. NSE seems to be a clinically worthwhile serum tumour marker for monitoring seminoma patients, with a sensitivity and specificity of the same order as HCG.     

Tumour marker concentration at the start of chemotherapy is a stronger predictor of treatment failure than marker half-life: a study in patients with disseminated non-seminomatous testicular cancer.

We investigated the prognostic value of the serum half-life of human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP) during induction chemotherapy and the relative prognostic importance of initial marker concentrations and marker half-life. Marker half-lives were calculated using two abnormal values observed between day 8 and day 22 of the first chemotherapy cycle. Moreover, analyses were carried out using day 43 as the second measurement point. Treatment failure at any time was chosen as the end point. The relative prognostic influence of marker half-lives and initial marker concentrations was tested in univariate and multivariate analyses. Half-lives were considered to be prolonged if > 3 days for HCG and > 6 days for AFP. In addition, we separated patients into those with half-lives > 6 days for HCG and those with half-lives > 10 days for AFP to examine whether these long half-lives were associated with a poor prognosis. A group of 669 patients treated with cisplatin combination chemotherapy was studied. Forty-two per cent of the patients had normal HCG and 37% had normal AFP at the start of chemotherapy. At day 22, HCG was still elevated in 138 patients and AFP in 211. At day 43, the numbers of these patients were 35 and 80 respectively. Based on the measurements obtained on day 8 and day 22, a half-life of HCG > 3 days or > 6 days and/or a half-life AFP > 6 days or > 10 days did not accurately predict treatment failure (P=0.413 and P=0.851, respectively; values obtained using tests for trend). However, initial marker concentrations of HCG and/or AFP > 1000 IU l(-1) were highly significant prognosticators for treatment failure (P=0.001 and P < 0.001 respectively), independent of half-life values. Half-lives calculated with the values obtained on day 43 did not contribute to the accuracy of the prediction of treatment failure. We conclude that half-lives of HCG and AFP during induction chemotherapy are inaccurate parameters for the prediction of treatment failure. In contrast, initial serum concentrations of HCG and AFP are highly significant in the prediction of unfavourable treatment outcome.     

Prognostic Factors in Testicular Germ Cell Tumours Experiences from 1058 Consecutive Cases

Prognostic factors in carcinoma of the testis were studied in 1058 adult patients treated in Denmark from 1976 to 1980. Separate analyses of the prognostic factors were carried out within the subgroups formed by a classification of the patients according to main histologic type (seminoma, non-seminoma) and the clinicoradiologic stage (I, II and III). The prognosis was measured by relapse-free survival (stage I and II), and survival (stage II and III). The prognostic value of 19 clinical and histologic parameters was evaluated using logrank tests and multiple regression analyses. An elevated HCG level and the size of retroperitoneal metastases were associated with a significantly adverse prognosis for seminoma in stage II. For non-seminomas the following parameters had a singificant influence on the prognosis. Stage I: postoperative HCG level, local invasion and number of mitoses. Stage II: size of retroperitoneal metastases, postoperative HCG level, tumour size and local invasion. Stage III: presence of liver or lung metastases, postoperative HCG level, presence of choriocarcinoma or endodermal sinus tumour, and age.     

Testicular cancer in young Norwegians

The clinical experience is reviewed in 597 Norwegian testicular cancer patients (age range: 15-45 years) treated from 1979 to 1986. During this period, computer tomography, determination of serum AFP/HCG, and cisplatin-based chemotherapy represented the modern diagnostic and therapeutic modalities. Before orchiectomy 67% of the patients had elevated AFP/HCG. An abnormal postorchiectomy serum tumour marker decrease and the presence of small vessel infiltration in the histological sections of the primary tumour significantly predicted microscopic retroperitoneal metastases in patients with clinical stage I (CSI) nonseminoma. One-third of these patients had a pathological stage II (PSII). After radiotherapy 99% of 90 seminoma patients (CSI/IIa) survived for 5 years. After cisplatin-based chemotherapy (+radiotherapy/surgery) the 5-year survival rate in 25 patients with advanced seminoma was 81%. The survival rate in 148 nonseminoma patients PSI/IIa was 100% and 87% in 94 patients with advanced nonseminoma (greater than or equal to CSIIb). Nausea, general exhaustion, myelosuppression, peripheral neuropathy, and Raynaud-like phenomena were the main acute treatment-related side effects. Slight gastrointestinal problems, slight peripheral neuropathy, Raynaud-like phenomena, and fertility disturbances were frequent late side effects. The sexual life in testicular cancer patients did not seem to be significantly impaired as compared to the normal population. Most of the patients reported no or only slight emotional problems during and after treatment. The need of thorough information at the time of diagnosis was stressed by most of them. Secondary cancer was diagnosed in 27 of 795 patients (1970-1982) (Testicular: 15; pulmonary: 4; sarcoma: 2; others: 6). Testicular cancer is today a curable malignancy. Future clinical research has to concentrate on the identification of high-risk and low-risk patients, the avoidance of overtreatment, and the reduction of toxicity (especially of long-term side effects).     

Tumor markers in testicular tumors

Serum levels of hCG, AFP, CEA and testosterone were measured in 20 patients with testicular tumors for an evaluation of their clinical significance as tumor markers. HCG was elevated in those with chorional and syncytiotrophoblastic cell tumors, but it was also detected in some cases of embryonal carcinoma and seminoma, suggesting the presence of hCG-producing elements. AFP was exclusively elevated in embryonal and yolk sac tumors. CEA and testosterone were mostly normal in all patients. HCG and AFP fluctuated in good correlation with the clinical course. Thus, hCG and AFP were valuable tumor markers for testicular tumors for the diagnosis of histological type and stage and monitoring the therapeutic effect and prognosis.     

Prognostic Significance of Marker Half-life during Chemotherapy in Non-seminomatous Germ Cell Testicular Tumors

Decrease in serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels is considered as a response during chemotherapy of non-seminomatous germ cell testicular tumors, but data on the prognostic significance of marker half-life remains inconclusive. Serum marker half-life was evaluated in 34 patients with elevated markers, receiving chemotherapy (CT). Marker half-life was calculated from the natural logarithm of the sequential AFP or HCG concentrations. The correlation between event-free (EFS) and overall survival (OS) with unfavorable half-lives of AFP and HCG was evaluated. Median actual half-life (AHL) AFP was 3.9 days (range, 1.4-21.5) and median AHL HCG was 4.4 days (range, 1.4-21.0); 82% of the patients had a satisfactory initial decline in AFP, and 71% had a satisfactory initial decline in HCG. There was a significant difference in EFS and OS between the two groups of patients with an AFP half-life 7 days. HCG half-life did not adversely affect EFS and OS. The correlation of better EFS and OS with appropriate AFP marker half-life during chemotherapy could provide a dynamic method, which could complement the standard baseline prognostic factors, for the prediction of prognosis.     

Utility of serum tumor markers during surveillance for stage I seminoma

BACKGROUND:

The serum tumor markers α‐fetoprotein (AFP), β‐human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) are often measured as part of surveillance protocols in patients with stage I seminoma. In this study, the authors evaluated the utility of routine measurement of these markers in the detection of disease relapse.

METHODS:

Data were gathered from a prospectively maintained database of patients who underwent surveillance for stage I testicular seminoma diagnosed between 1982 and 2005 at Princess Margaret Hospital. Patients were followed on a predefined schedule with physical examination (PE), serum tumor markers, abdominopelvic computed tomography, and chest x‐rays. The records of patients who relapsed were examined for details of imaging and serum tumor markers throughout the period of follow‐up until the time of relapse.

RESULTS:

Of the 527 patients who were managed by surveillance, 75 patients (14%) relapsed at a median follow‐up of 72 months. Of these, 65 patients relapsed within the first 3 years and had routine serum tumor markers measured. In total, 11 patients had abnormal tumor markers at the time of relapse (AFP, 0 patients; HCG, 6 patients; LDH, 4 patients; and HCG and LDH, 1 patient). Only 1 patient had an elevated tumor marker (LDH) before relapse, as defined by an abnormal imaging study (n = 64) or physical examination (n = 1), for which the treatment and outcome were not affected.

CONCLUSIONS:

Serum tumor marker levels did not aid in the early diagnosis of disease relapse in patients with stage I seminoma who were managed with surveillance. The current results indicated that routine measurement of serum tumor markers can be discontinued safely in seminoma surveillance schedules. Cancer 2012. © 2012 American Cancer Society.     

Acute changes of alpha-fetoprotein and human chorionic gonadotropin during induction chemotherapy of germ cell tumors

Thirty-seven consecutive patients with germ cell cancers (34 testicular, three extragonadal) and elevated serum levels of alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG) were treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum induction chemotherapy. The AFP and/or HCG normalized in 36 patients. The AFP half-life was 7.9 days between Days 1 and 21 postchemotherapy but 6.0 days between Days 21 and 42 (p less than 0.05). The prolonged AFP half-life between Days 1 and 21 was related to a median increase of 57.5% (range, 22 to 219%) in the AFP level. This increase in the marker value occurred between Days 2 and 9 of therapy (median, Day 5). There was also a median increase of 181% (range, 27 to 600%) in the HCG level at a median of 5 days after the start of therapy. The increase in the AFP and HCG levels occurred in 63 and 70% of evaluable patients, respectively, and correlated with the presence of a large volume of metastatic disease (chi 2 = 8.87). Patients with relapsed or refractory disease had prolongation of the AFP half-life between Days 21 and 42 as compared to nonrelapsed patients. AFP and HCG half-life calculations should be used in the management of patients with germ cell cancers.     

Correlation of serum tumor markers in advanced germ cell tumors with responses to chemotherapy and surgery

Remission rates induced by chemotherapy alone or by combined chemotherapy and surgery were analyzed in relation to specific serum tumor marker abnormalities immediately before treatment in 103 patients with Stage III or bulky Stage II nonseminomatous germ cell tumors. Complete remission occurred in 92% (12 of 13) of patients with normal levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), in 26% (6/23) with elevated AFP only, in 46% (13/28) with elevated HCG only, and in 39% (13/36) with abnormalities of both AFP and HCG. Patients with elevated AFP less frequently had a complete remission (CR) to chemotherapy (CR, 34% versus 61% with normal AFP), but benefitted from adjunct surgery (CR, up to 59%). Patients with very high (greater than 1000 ng/ml) serum AFP or HCG responded poorly to chemotherapy (CR, 17%) but especially large tumor burdens may have contributed to these unfavorable responses. Patients with both minimal and advanced metastatic disease had higher CR rates if they had serum tumor marker levels below rather than above 1000 ng/ml. Adjunct surgery eliminated the correlation between the "poor prognostic factors" associated with specific marker abnormality and an incomplete response to chemotherapy by rendering a significant number of such patients free of disease through resection of residual metastatic deposits.     

Serum alpha1-foetoprotein levels in 153 male patients with germ cell tumours.

--alpha1-Foetoprotein (AFP) levels have been measured by radioimmunoassay in the serum of 153 male patients with gonadal and extragonadal germ cell tumours. Thirty-five patients with pure seminoma, and 34 patients with teratoma but without any postoperative evidence of residual or recurrent tumour, consistently had normal serum AFP levels (less than 25 ng/ml). Of 84 patients with active teratomas, 56 (67%) had serological evidence of AFP production. Ten patients with histological evidence of pure yolk sac (endodermal sinus) tumours all had raised levels. Teratomas containing yolk sac (elements may or may not be associated with raised serum levels. Trophoblastic (choriocarcinomatous) elements in a teratoma were not normally associated with high values. Fourteen patients with teratomas had elevated levels in the absence of histologically detectable yolk sac elements. Serum AFP levels often became elevated before clinical evidence of recurrence, so that AFP can act as an effective marker of the course of the disease and its response to therapy in many patients, but recurrent or progressive disease may be present in the absence of raised levels.     

Alpha-1 antitrypsin (AAT) and alphafoetoprotein (AFP) in sera of patients with germ-cell neoplasms: value as tumour markers in patients with endodermal sinus tumour (yolk sac tumour).

Serum alphafoetoprotein (AFP) and serum alpha-1 antitrypsin (AAT) were determined in 24 patients with germ-cell neoplasms of the gonads and extragonadal sites and in two patients with hepatocellular carcinoma. In the majority of the patients serial determinations were performed. All seven patients with testicular seminoma and four patients without evidence of active disease had normal levels of serum AAT and AFP. The remaining 13 patients with germ-cell neoplasms had tumours containing endodermal sinus tumour (yolk-sac tumour) elemetns. All these 13 patients had elevated levels of serum AFP and the levels were high or very high in most cases. Nine of these 13 patients had raised serum AAT, although the elevation above normal levels was only slight in a number of cases. When serial determinations were performed serum AAT levels frequently followed the pattern of serum AFP levels, but the AAT levels were frequently within normal limits and therefore the interpretation of the results was difficult, and much less reliable as compared with those for serum AFP. The elevation of serum AAT levels following the recurrence of the tumour was found to occur much later and was much less marked than elevation of serum AFP, which occurred early, showed a large rise and was a reliable marker of tumour recurrence in patients with germ-cell neoplasms containing endodermal sinus tumour elements. It is therefore considered that, although there is good evidence that serum AAT is produced by endodermal sinus tumour elements, serum AAT is not a useful monitor of disease activity in these patients, especially when compared with serum AFP, the value of which is well recognized. Serum AAT may be a useful tumour marker in patients with hepatocellular carcinoma, and this aspect should be investigated further.     

Elevated urinary transforming growth factor-beta1 level as a tumour marker and predictor of poor survival in cirrhotic hepatocellular carcinoma.

To assess the clinical relevance of transforming growth factor-beta1 (TGF-beta1) in hepatocellular carcinoma (HCC), urinary TGF-beta1 and serum alpha-fetoprotein (AFP) were determined in 94 patients with cirrhotic HCC, 94 age- and sex-matched patients with cirrhosis alone and 50 healthy adults. TGF-beta1 level in HCC was higher than in cirrhosis alone or in healthy controls (each P = 0.0001). There is an inverse correlation between TGF-beta1 and AFP levels (r = -0.292, P = 0.004). Significantly higher TGF-beta1 level was found in HCC patients with worsening Child-Pugh stages, diffuse HCC, tumour size > 3 cm, multilobular tumour and AFP < or = 20 ng ml(-1). TGF-beta1 level decreased after complete treatment with transcatheter arterial chemoembolization (P = 0.0001). The median survival in HCC patients with raised TGF-beta1 was shorter than those with normal TGF-beta1 (P = 0.018). Multivariate analysis indicated that TGF-beta1 and AFP were significantly correlated with the presence of HCC. In addition, TGF-beta1 could be used as a diagnostic marker for HCC, particularly in tumours with low AFP production. In conclusion, elevated urinary TGF-beta1 level is a tumour marker and predictor of poor survival for cirrhotic HCC.     

Brain metastases in malignant teratoma: a review of four years' experience and an assessment of the role of tumour markers.

Between 1973 and 1977, 247 patients with malignant teratoma have been treated in two units in London. Seventeen have developed brain metastases, an overall incidence of 6.2%. The median survival from diagnosis of cerebral metastases is 6 weeks and all patients except one have died. The survivor is disease-free 12 months after completing treatment, which included extensive use of chemotherapy, surgery and radiotherapy. Serum gonadotrophin (HCG) and alpha-foetoprotein (AFP) estimations have been performed in 264 patients as a means of monitoring the effects of therapy. In 42 patients (37 of whom had Stage IV disease) the peak HCG level was greater than 10(4) iu/l, and the incidence of brain metastases in this group was 26%, significantly higher than in the group with HCG levels below 10(4) iu/l, for which the incidence of cerebral deposits was 1.8% (P less than 0.0001). No significant correlation was seen between peak AFP levels and the incidence of brain metastasis. With the aim of improving results by earlier diagnosis, cerebrospinal fluid (CSF) specimens have been examined for HCG and AFP levels in 56 subjects, 9 of whom had brain metastases. A serum: CSF HCG ratio less than 40 is an accurate indication of the presence of brain metastases, and may have considerable predictive value. However, false-negative serum: CSF HCG rations (greater than 40) frequently occur in patients with proven brain deposits. Estimation of AFP in spinal fluid has not contributed to the early diagnosis of brain metastases in malignant teratoma.     

Diagnosis and treatment of mediastinal teratoid tumors

Among anterior mediastinal tumors affecting male patients of around 20 years old, mediastinal malignant teratoid tumor must be considered as one of the possibilities. Malignant teratoid tumor can be classified as seminoma, non-seminoma or mixed, according to clinical behavior. In the non-seminoma group, AFP and/or HCG can be the specific markers in the diagnosis or assessment of the effect of treatment. Chemotherapy with CDDP must be the first choice of treatment in these types of tumor, just as chemotherapy is the first choice of therapy in the treatment of small cell lung cancer, and surgery must be the adjuvant treatment to chemotherapy. On the other hand, seminoma can be treated by surgery and radiation, which has been proven to yield a good prognosis. In cases of seminoma which produces HCG and/or AFP, chemotherapy with CDDP must be added to surgery and radiation as in non-seminomatous mediastinal teratoid tumors, because the production of such markers in seminoma is considered to be one of the poor prognostic factors in the treatment of seminomatous mediastinal teratoid tumors.     

Tumor markers at the time of recurrence in patients with germ cell tumors

BACKGROUND: alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) closely follow the course of germ cell tumors (GCTs) and are widely used for diagnosis, prognosis, and follow-up purposes. The objective of this study was to assess the concordance of tumor markers at the time of diagnosis and recurrence. METHODS: The authors reviewed the records of 794 patients with GCTs treated in three Spanish hospitals from 1977-1996 and analyzed the concordance between AFP, HCG, and LDH levels at diagnosis and first and second recurrence. A positive marker was defined as a level of AFP > 10 ng/mL, HCG > 5 IU/L, or LDH > the upper limit of normal. One hundred twenty-five patients were identified who developed a first recurrence (123 had marker levels recorded). The median age was 27 years (range, 14-78 years). Histology was seminoma in 36 patients (29%) and nonseminomatous GCT (NSGCT) in 87 patients (71%). RESULTS: Seventy-nine patients (64%) had elevated tumor markers at diagnosis and 76 (62%) at first recurrence. An elevated marker was present at first recurrence in 58 of 79 patients (73%) with initially positive markers and in 18 of 44 patients (41%) with initially negative markers. In 84 of 123 patients (68%), the same marker pattern (positive or negative) was present at the time of diagnosis and at first recurrence, 78% in seminomas and 64% in NSGCTs. The earliest indicator of recurrence was an elevated marker in patients with NSGCTs and a radiologic finding in patients with seminomas. Thirty patients developed a second recurrence, 27 of whom (90%) had the same marker pattern as at first recurrence. CONCLUSIONS: Tumor marker pattern at diagnosis is not a good predictor of the pattern at recurrence, particularly in patients with NSGCTs. Marker assessment should be included in the follow-up schedule regardless of levels at the time of diagnosis. Early detection of recurrence should not rely only on marker levels, even in patients with elevated levels at presentation.