Nasser Javadpour

The Value of Serum Tumor Markers in the Staging and Prognosis of Germ Cell Tumors of the Testis

AbstractDuring a 3-year prospective study serum chorionic gonadotropin, alpha-fetoprotein and plasma carcinoembryonic antigen were measured in 111 patients with germ cell tumors of the testis. Either human chorionic gonadotropin or alpha-fetoprotein levels were elevated in 91 per cent of the patients with clinically demonstrable non-seminomatous tumors. Among 24 patients who had recurrent disease 16 (67 per cent) had elevated alpha-fetoprotein or human chorionic gonadotropin at a time when recurrence was clinically undetectable. All patients free of tumor had normal levels of human chorionic gonadotropin or alpha-fetoprotein, there being no falsely positive values. Carcinoembryonic antigen was elevated in 33 per cent of patients with seminoma and in 7 per cent of patients with non-seminomatous tumor but carcinoembyonic antigen levels did not correlate with the course of the disease. Determinations of human chorionic gonadotropin and alpha-fetoprotein before lymphadenectomy decreased the error in clinical ...

Treatment of poor prognosis nonseminomatous testicular cancer with a “high‐dose” platinum combination chemotherapy regimen

A new intensive four drug combination chemotherapy regimen, termed PVeBV, consisting of cis‐platinum, vinblastine, bleomycin, and VP‐16, was administered to six previously untreated patients with poor prognosis advanced nonseminomatous testicular cancer and to four patients who had relapsed on primary platinum based regimens. The cis‐platinum was administered in 250 ml of 3% saline at twice the dose (40 mg/m2 IV days 1–5 every three weeks) used in other treatment schedules. All six previously untreated patients achieved a complete remission. Four achieved a complete remission with three cycles of PVeBV while the other two patients achieved a complete remission with an additional cycle of cisplatinum and VP‐16 at 200 mg/m2 IV × five followed by autologous bone marrow infusion. All four relapsed patients responded to PVeBV (two complete remissions and two partial remissions). There were no deaths associated with PVeBV therapy; however, myelosuppression was severe. There has been no renal toxicity (other than hypomagnesemia) observed with 35 cycles of high‐dose platinum therapy in previously untreated patients. These results indicate that PVeBV is a promising chemotherapy regimen for the treatment of poor prognosis testicular cancer patients. Furthermore, it appears that cis‐platinum can be administered at higher doses than previously used without an increase in renal toxicity if administered in hypertonic saline. The high‐dose cis‐platinum schedule, as used in PVeBV, warrants evaluation in other tumors which respond to standard‐dose platinum therapy.

The role of biologic tumor markers in testicular cancer.

Serial quantitative measurements of serum alphafetoprotein (AFP) and human chorionic gonadotropin (HCG) have been prospectively studied in 386 patients with testicular germ cell cancer during the past seven years using sensitive and specific radioimmunoassays (RIAS). When HCG and AFP was measured in patients with nonseminomatous testicular tumors (NSTT), about 90% of these patients with active tumors have elevated levels of serum HCG and/or AFP.

The cell surface antigen A, B or O(H) as an indicator of malignant potential in stage A bladder carcinoma: preliminary report.

The presence or absence of cell surface antigens (A,B and H) on the cell surface of bladder tumors has been studied. The major blood group antigens A, B or O(H) are present on normal bladder epithelium but are not present on some low grade and low stage papillary transitional cell carcinomas of the bladder. We have demonstrated that of 5 stage A bladder tumors that have not recurred in at least 5 years 3 retained the cell surface antigens, while tumors that have recurred locally, invaded or metastasized had lost these cell surface antigens on the original stage A tumor.

Testicular Germ-Cell Neoplasms: Recent Advances in Diagnosis and Therapy

The diagnosis and treatment of testicular neoplasms have been facilitated by identification of the tumor-associated proteins alpha-fetoprotein and human chorionic gonadotropin. These circulating tumor markers, present in 85% to 90% of patients with nonseminomatous testicular cancer, reflect tumor presence and reliably indicate response to therapy. Alpha-fetoprotein is produced by embryonal carcinoma and yolk-sac tumors; human chorionic gonadotropin is produced by syncytiotrophoblastic giant cells and the syncytiotrophoblastic component of choriocarcinoma. Refinements in staging techniques and definitions have improved prognostication. Effective therapy for seminoma (cure rate, greater than 90%), early-stage (stage I, stage IIN1-2) testicular carcinoma (cure rate, 65% to 87%), and advanced (stage IIN3-4, stage III) testicular carcinoma (complete remission rate, 50% to 74%) has been shown in clinical trials. Adjuvant chemotherapy/radiotherapy trials for limited stages of testicular carcinoma, and further experience with intensive chemotherapy-based trials for advanced stages may further improve the prognosis for all testicular germ-cell neoplasms.

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 radio‐immunoassay. 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. Cancer 42:2768–2772, 1978.

Familial testicular cancer and urogenital developmental anomalies.

In a case‐control study of testicular cancer, 6 of 269 cases (2.2%) reported a first‐degree relative with testicular cancer, compared to 1 of 259 controls (0.4%). Fathers and brothers of testicular cancer cases had a six‐fold elevated risk of developing a testicular malignancy compared to men in the general population. Cryptorchidism was reported in a first‐degree relative in 1 (17%) of the familial cases versus 7 of 259 (2.7%) controls and 14 of 263 (5.3%) cases with a negative family history for testicular cancer. One half of the 6 familial cases reported a first‐degree relative with a groin hernia (all surgically repaired before age 12), compared to 12.7% of 259 controls and 10.3% of 263 nonfamilial cases. Three familial clusters identified through the case‐control study were selected for clinical evaluation. One of the 6 surviving males with testicular cancer in these 3 families had undergone orchiopexy and inguinal herniorrhaphy at age 6 years, and one had a hydrocele associated with his testicular tumor. Of the 12 living fathers and brothers of these 6 men, 3 reported childhood inguinal hernias, two with coexisting hydroceles. One additional hernia and two additional hydroceles were detected during urologic evaluation of these healthy relatives. The high prevalence of cryptorchidism, inguinal hernias, and hydroceles among men in these families suggests that an underlying alteration in urogenital embryogenesis may be associated with the familial predisposition to testicular neoplasia.

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 chroiomic 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.

Germ‐cell tumors in patients with apparently normal testes

Germ‐cell tumors occasionally occur in patients with clinically normal testes. Although data exist correlating serial serum hCG and AFP in germ‐cell neoplasms of testicular origin, the literature is sparse concerning the patients presenting with clinically normal testes. Presented in this report are data to confirm the reliability and usefulness of serial serum hCG and AFP levels in those patients with extragonadal germ‐cell tumors and apparently normal testes. Six patients with nonseminomatous extragonadal tumors are presented. Serial serum hCG and AFP levels correlated with the clinical course in each of the patients. The serum hCG and/or AFP decreased with response to therapy and increased with progression of disease. It is concluded that serial serum hCG and AFP determinations are very useful parameters to evaluate and follow the course of disease in this group of patients.

Significance of elevated serum alphafetoprotein (AFP) in seminoma

Serial serum determinations and cellular localization of AFP utilizing radioimmunoassay and immunocytochemical techniques have improved the diagnosis and therapy of testicular seminoma. Elevated level of serum AFP in patients with “pure seminoma” suggests the presence of non‐seminomatous elements or liver metastases. It appears that modest elevated serum alphafetoprotein may be encountered in liver metastases when active liver regeneration is present. These distinctions are pertinent and may play an important role in selecting therapeutic modalities. Two patients are reported to illustrate the interpretation of elevated AFP in patients with testicular seminoma.