UPDATE IN CANCER CHEMOTHERAPY: GENITOURINARY TRACT CANCER, PART 4: TESTICULAR CANCER Jane C. Wright, MD Valhalla, New York An update of the state of the art of cancer che- is associated with accurate serum markers: human motherapeutic treatment of genitourinary tract chorionic gonadotropin (HCG) and a-fetoprotein cancer is described in this multi-part series: in- (AFP). In addition, in these cancers it is possible to cluded are cancers of the kidney, bladder, pros- convert a chemotherapy-produced partial remission tate, testicle, ovary, uterus, vulva, and gestational into a complete remission by the surgical removal of trophoblastic neoplasms. Part 4 is a review of the residual disease. Of further interest is the change treatments for cancer of the testicles. that occurs in the histology of these tumors from an Testicular cancer is highly curable and re- aggressive embryonal-cell carcinoma in the orchiec- sponds well to both surgery and chemotherapy. tomy specimen to a mature teratoma in the surgical Patients with stage I and stage 11 nonsemino- specimen following the administration of chemo- matous germ-cell tumors may be cured by sur- therapy. Of most significance is that testicular cancer gery alone or in combination with chemotherapy. has become a highly curable disease that now repre- In patients with pathologic stage 11 disease, the sents a model for a curable neoplasm. use of adjuvant chemotherapy with two courses While the cause of testicular cancer is unknown, of platinum-based combination drugs has been there are certain conditions associated with an in- successful in preventing relapse. Further refine- creased appearance of these tumors, such as in the ments in management and research could banish testes following mumps orchitis and in the atrophic the problem of testicular cancer. cryptorchid testes (undescended testes) even after or- chiopexy. In the undescended testes, the risk of de- veloping cancer is 40 times greater than in the normal descended scrotal testes. Testicular cancers are rare tumors that account for There have been major differences of opinion and only 1 percent of all the cancers that occur in men controversy concerning the topic of the histologic and have an annual incidence of 2.3 persons per classification of testicular tumors. Since 1940 there 100,000 in the United States. These tumors are of have been six major reclassifications. There are four major importance because they are the most common classical histologic cell types in the testicular tumor: carcinomas in young men in the 15- to 35-year-old seminoma, embryonal carcinoma, teratoma, and age group. Unlike many neoplasms, testicular cancer choriocarcinoma. Of the four types 40 percent are seminomas, 15 to 20 percent are embryonal carci- nomas, 20 to 25 percent are teratocarcinomas, and 1 Dr. Wright is Professor Emeritus of Surgery, New York Medical percent are choriocarcinoma. A comparison of clas- College, Valhalla, New York. Requests for reprints should be addressed to Dr. Jane C. Wright, 315 West End Avenue, New sifications of testicular germ-cell tumors is shown in York, NY 10023. Table 14.204 In the British system, all nonsemino- JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 80, NO. 4, 1988 425 CANCER CHEMOTHERAPY UPDATE TABLE 14. CLASSIFICATIONS OF TESTICULAR GERM-CELL TUMORS* British Testicular2O8 Dixon and Moore201 Mostofi and Price206 World Health Organization207 Tumor Panel Seminoma Tumors of one histologic Tumors of one histologic type type Seminoma (typical) Seminoma Seminoma Spermatocytic seminoma Spermatocytic seminoma Spermatocytic seminoma Anaplastic seminoma** Embryonal carcinoma Enbryonal carcinoma Embryonal carcinoma Malignant teratoma, Polyembryoma Polyembryoma undifferentiated Adult Teratoma, adult Teratoma Teratoma Teratoma, differentiated Mature Mature Immature Immature With malignant With malignant transformation change*** Embryonal carcinoma ju- Yolk sac tumor (embryonal car- Yolk sac tumor venile cinoma, juvenile type, en- dodermal sinus tumor) Choriocarcinoma Choriocarcinoma Choriocarcinoma Tumors of more than Tumors of more than one histo- one histologic type logic type Teratoma with em- Embryonal carcinoma Embryonal carcinoma with tera- Malignant teratoma, in- bryonal carcinoma with teratoma ("ter- toma ("teratocarcinoma") termediate ("teratocarci- atocarcinoma") noma") Specify types Choriocarcinoma and any other Malignant teratoma tro- types (specify type) phoblastic Specify types Other combinations (specify) "Combined tumor" when seminoma is present * From Einhorn LH204; excluding extratubular germ-cell neoplasia. ** This term has been discarded in a more recent formulation. *** Refers to malignant areas independent of seminoma, embryonal carcinoma, or choriocarcinoma. matous germ-cell tumors are malignant teratomas of pain in the testes, especially after "trauma" in the one type or another. In the American system, the young adult. Other signs and symptoms are related term embryonal carcinoma indicates a tumor that to metastatic disease and include abdominal mass, appears as the most undifferentiated form of tera- adenopathy, gynecomastia, headaches, and other toma. The importance of the classification system is central nervous system symptoms. that in most of the large series of cases of testicular The diagnosis of testicular cancer is confirmed tumors treated by radiation therapy, the tumors are usually by orchiectomy, which is performed surgically classified according to the British system; however, through a high inguinal approach that allows for de- in the reports of the large surgical series, the tumors livery of the testes without contamination of the ad- are classified according to the American system.205 jacent scrotal tissue. If the diagnosis is made, a com- Ninety-six percent oftesticular tumors are malignant plete workup is done to stage the disease. This workup germ-cell tumors, and for the purposes of treatment includes chest films, tomography (ifthe serum mark- they are considered as either seminomas or as non- ers are elevated), intravenous pyelogram, abdominal seminomas. sonography, computerized axial tomography, serum The presenting sign of testicular cancer is usually a-fetoprotein, and ,B-subunit HCG. a-Fetoprotein, a a painless scrotal mass, and there may be swelling or serum protein in the embryo, is found in approxi- 426 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 80, NO. 4, 1988 CANCER CHEMOTHERAPY UPDATE mately 70 percent of patients with teratocarcinomas percent false-negative rate,2"' including the scans and and embryonal-cell carcinomas. In addition, AFP is serum markers. found in 70 percent ofpatients with hepatomas and, occasionally, in cases of other gastrointestinal tract carcinomas (eg, pancreas, gallbladder, etc). Because TREATMENT the half-life ofAFP is five days, it is necessary to wait Surgery, radiotherapy, and chemotherapy are all more than five days after orchiectomy for the serum useful in the treatment of patients with testicular tu- level to return to normal to be certain that the patient mors. Coordinated treatment with these modalities does not have metastatic disease. Human chorionic has led to the marked improvement in the survival gonadotropin, a glycoprotein, is composed of two rates over the past 25 years. polypeptide chains known as alpha and beta. The ,3 subunit is unlike the ,3 subunits of luteinizing hor- mone, follicle-stimulating hormone, and thyroid- Surgery stimulating hormone, but the a subunit is similar to Surgery is used in the treatment of the primary the a subunits ofthese three hormones. Patients with tumor, for regional lymphatic metastasis and, on oc- germ-cell tumors are best followed by radioimmu- casion, for the management of distant metastases. noassays using antibodies against the ,B subunit. The After the diagnosis is made, the primary tumor should metabolic half-life ofHCG is 30 hours. a-Fetoprotein be removed immediately. Radical orchiectomy is the or HCG is positive in 85 percent ofpatients with tes- procedure ofchoice for the early stages ofthe disease ticular tumors; however, these markers should not be because it removes all ofthe tumor. The orchiectomy relied on alone for staging. includes a high-inguinal ligation of the vas deferens and spermatic vessels, a complete removal of the contents of the inguinal canal, and removal of the STAGING OF TESTICULAR TUMORS testis and its adnexa, including the parietal layer of the tunica vaginalis. Removal ofthe entire testis per- Testicular tumors are staged from I to III according mits serial sections to determine the histopathologic to the progression ofthe disease. In stage I, the disease diagnosis. The cure rate for seminomas is in the 90 is confined to one testis IA. In stage IB, the disease is to 95 percent range with primary orchiectomy fol- as in IA, with the addition of histologic evidence of lowed by postoperative radiation therapy; however, metastases to the iliac or para-aortic nodes. In stage for nonseminomatous tumors, the cure rate has II disease, there is clinical or radiographic evidence ranged from 15 to 50 percent. of metastases to the femoral, inguinal, iliac, or para- Because testicular cancers usually spread first by aortic nodes, but no evidence of disease above the the lymphatics to the retroperitoneal lymph nodes, diaphragm. There has been controversy over whether many clinical groups remove the nodes as well. The exploratory laparotomy and node dissection should radical retroperitoneal lymphadenectomy (RPLND) become a mandatory staging procedure