Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Testicular cancer H. Bruce Vogt MD & Michael S. McHale MD To cite this article: H. Bruce Vogt MD & Michael S. McHale MD (1992) Testicular cancer, Postgraduate Medicine, 92:1, 93-101, DOI: 10.1080/00325481.1992.11701393 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701393
Published online: 17 May 2016.
Submit your article to this journal
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [RMIT University Library]
Date: 15 June 2016, At: 18:47
Symposium
Second of four articles on urologic problems
(and much larger) between ages 20 and 35. Malignant testicular neoplasms are rare after age 40, and if found in a patient over age Role of primary care physicians in screening 50, lymphoma should be susand education pected. Although the incidence of testicular cancer is increasing, 2'7 monality rates are improving because of successful treatment. In 1977, this disease was the third leading cause of cancer death in men aged 15 to 34; today, it is Preview not among the top five causes.3.4.6 The typical attitude of the young is that serious disease is The major predisposing factor for older folks. However, this is clearly untrue in the case of to development of testicular cantesticular cancer, which largely affects teenagers and young cer is cryptorchidism, which conadults. Since its only sign may be a painless mass, physical fers a risk 2.5 to 40 times that examination by physicians and by the patients themselves is found in the general population. 8 of utmost importance. The authors summarize screening for the disease and treatment methods, which are chosen on the The incidence of malignant transformation in these patients basis of the stage of disease. has been reponed as ranging from 3% to 18% (mean, 11 %) .9 Giwercman and associates 10 conerative techniques, and highly H. Bruce Vogt, MD cluded from their studies and effective systemic chemotheraMichael S. McHale, MD other Scandinavian studies that peutic agents. 3· 5 The major role the true incidence is between 2% of primary care physicians in •) Although it is a relatively rare and3%. management of testicular cancer disease, testicular cancer is the The risk is panicularly high in is in educating young men on most common type of cancer in 12 patients with an intra-abdominal the dangers of the disease and on men aged 15 to 35. ' Dramatic how to perform self-examination. testis. 11 Although cancer usually advances in its treatment have develops in the undescended made testicular cancer a model testis, in 15% to 20% of cases it Predisposing factors for curable, solid, malignant occurs in the contralateral, norAbout 6, 100 new cases of testicuneoplasms. These advances inmally positioned testis, which lar cancer/ or 4 per 100,000 popcluded the development of radiosuggests an underlying testicular ulation/ are reponed annually in immunoassays for sensitive tu78 defect. Whether orchiopexy at a • United States. The disease the mor markers and an integrated young age reduces subsequent has two peaks in frequency: one approach to management comnot been established, but risk has in early childhood and another bining irradiation, improved op-
Postgraduate Medicine 1992.92:93-101.
Testicular cancer
continued
VOL 92/NO 1/JULY 1992/POSTGRADUATE MEDICINE • 'RSTICULAR CANCER
93
Postgraduate Medicine 1992.92:93-101.
The vast majority of primary testicular tumors are of germ cell origin and are malignant.
rhe procedure should be completed ro allow careful follow-up of patients with cryptorchidism. Intra-abdominal testes should be removed. 2 Additional risk factors include previous cancer in the opposite testis, a history of mumps orchitis, inguinal hernia or hydrocele in childhood, family history of cryptorchidism, white race, and a high socioeconomic srarus. 2·4An increased prevalence is also seen in patients with gonadal dysgenesis and in those with Klinefelter's syndrome (ie, XXY chromosome complement). 8 In one study, 12 rhe presence of supernumerary nipples was associated with an increased incidence. However, in most patients, no predisposing factor can be implicared.3·4
Classification of disease The vast majority (96%) of primary testicular rumors are of germ cell origin and are malignant.1'13 There are four classic cell types, which can be divided into five pathologic entities according to the Dixon and Moore classification: seminoma, embryonal carcinoma, teratoma (adult), choriocarcinoma, and teratocarcinoma (teratoma with embryonal carcinoma). Pure seminoma accounts for 40% of testicular cancers. 1'13 Seminona can be subclassified
94
as classic (or typical), anaplastic, or spermatocyric. 1'7 The spermatocyric type occurs in older patients, is the most common germ cell rumor after age 70, and has the highest incidence ofbilarerality.11 Embryonal carcinoma (which includes yolk sac or endodermal sinus rumors in some classification systems) accounts for 1So/o ro 20% of testicular cancers.w This is a very aggressive rumor, and many patients have metastatic disease when diagnosed. 11 Embryonal carcinoma is more common in infants and young children bur is more aggressive when seen in adults. 1 Teratomas contain elements from two or more of the germinal celllayers. 3·7 They are less aggressive than other nonseminomatous rumors bur do have merastatic potential. When mitotic figures are identified within the rumor, the teratoma is referred to as immature. 1 Choriocarcinoma, which accounts for 1o/o of testicular rumors, is the most malignant type. 13 Syncyriorrophoblasric cells must be identified histologically ro establish irs diagnosis. These cells are responsible for the secretion of human chorionic gonadotropin (hCG), an important rumor marker. 1 Non-germ cell rumors account for about So/o of testicular
cancers. 14 Of these, rete cord or gonadal stromal types predominate and include rumors of Leydig, Serroli, granulosa, theca, and mixed cell origin. Several malignant neoplasms have been described as metastasizing ro the testis. Perhaps rhe most important is lymphoma, because ir is nor unusual; ir represents So/o of all testicular rumors.14 Whether primary lymphoma can develop in the testis is controversial. The median age of these patients is 60, and 80% of them are over age 50. 14 The critical distinction for clinicians is whether a rumor is a seminomarous or nonseminomatous germ cell neoplasm. Patient screening Primary care physicians should include examination of the testes in their cancer screening activities. The US Preventive Services Task Force 15 specifically recommends screening in males with a history of cryptorchidism, orchiopexy, or testicular atrophy. The task force makes no recommendation for or against screening in males who are nor ar high risk, bur testicular examination should be performed during any screening physical if iris nor part of a planned preventive program. As noted, in most patients with cancer of the testis, no predisposing factor is identified. 3·4
TUTICULAR CANCIUI • VOL 92/NO 1/JULY 1992/POSTGRAOUATE MEDICINE
Postgraduate Medicine 1992.92:93-101.
Physical examinations for high school athletics and college entrance are excellent opportunities to educate young men on testicular self-examination.
Primary care physicians should take advantage of the office visit for a physical examination to provide patient education and promote testicular self-examination. Examples of excellent opportunities for such education include physical examinations for high school athletics and college entrance. Many young men are unaware of the existence of testicular cancer in their age-group. 16 Patients should be taught the technique of testicular self-examination2'3 and given a handout to reinforce the information. Among the useful available pamphlets are Testicular Self-Examination, published by the National Cancer Institute, and For Men Only. published by the American Cancer Society. To encourage early self-referral, physicians should stress as pan of their patient education the excellent prognosis associated with early treatment of testicular cancer. Although most patients have a favorable outcome, a poorer prognosis is seen with advanced disease, and there is a clear correlation between the interval from onset of symptoms to diagnosis and the stage of disease. 16
Clinical presentation The most common manifestation of testicular cancer is a painless mass.u' 13 '17 '18 The spectrum of complaints, however, is broad.
H. Bruce Vogt, MD Dr Vogt is professor of family medicine and dean of graduate medical education, University of South Dakota School of Medicine, Sioux Falls.
Some patients do have pain. Others report a heavy sensation in the scrotum1'2 or swelling or a change in the consistency of the testis. 24 Acute pain may be secondary to torsion or epididymitis3'4 or caused by intratesticular bleeding1or infarction. 11 Patients with advanced disease may present with weight loss, abdominal or back pain secondary to retroperitoneal adenopathy, or dyspnea from pulmonary metastases. 24 Gynecomastia may result from increased hCG levels. 24· 11 In a small study, Tseng and colleagues19 reported a 10% inci-
dence of gynecomastia or severe breast tenderness in association with elevated hCG. Other presenting symptoms or signs include infertility11 and, in advanced disease, supraclavicular adenopathy and urinary obstruction. 3'4
Diagnostic evaluation Differential diagnosis of a scrotal mass includes epididymitis, inguinal hernia, hydrocele, spermatocele, and testicular torsion. 2 Pain, fever, leukocytosis, and pyuria usually accompany epididymitis, and abrupt onset of severe pain is the hallmark of tor-
continued
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The tumor markers alpha fetoprotein and human chorionic gonadotropin are most useful for early determination of relapse in patients treated for testicular cancer.
my with pathologic examination. Before surgery, blood should be obtained for subsequent determinations of tumor markers if cancer is diagnosed.3.4
Postgraduate Medicine 1992.92:93-101.
Michael S. McHale, MD Dr McHale is a hematologistoncologist in private practice in Omaha.
sion. 2'18 Hydroceles and spermatoceles are painless, transilluminable masses. Primary care physicians should maintain a high index of suspicion when evaluating a scrotal mass. Abnormalities are best diagnosed by careful bimanual palpation. 11 Occasionally, a lesion of the testis may be indistinguishable from one of the epididymis. 18 Bilateral transscrotal ultrasonography can be of assistance in such cases,3•4•17'20 as well as when no palpable mass or only a minimally definable lesion is present.
96
A definite testicular mass must be considered malignant until proven otherwise, and the patient should be promptly referred to a urologist. 18 In their study, Einhorn and associates1 found that 55% of patients eventually found to have cancer were initially treated for epididymitis. Unfortunately, because of physician and patient delays, a 3- to 6-month period between initial symptom and diagnosis is common.7 Definitive diagnosis of testicular cancer is made by orchiecto-
TESncUL.AR
~R
Tumor markers Alpha fetoprotein and hCG are biologic tumor markers that are routinely used in the management of testicular cancer. 1'3'21 They can detect early or smallvolume disease but are most useful for early determination of relapse in previously treated patients.21 Alpha fetoprotein is a glycoprotein produced by cells of fetal origin. An increase in patients with pure seminoma has never been documented. Therefore, if it is detected, the patient must be treated as having nonseminomatous disease, regardless of the pathology. IJ.I? Alpha fetoprotein is commonly detected in embryonal carcinoma. 3 A glycoprotein produced by syncytiotrophoblasts,3'21 hCG is most often found in choriocarcinoma. However, it can be detected in embryonal carcinoma3 and in about 10% of cases of seminoma. 1It may stimulate testicular secretion of estrogen, resulting in gynecomastia. 3 No useful clinical marker has been found for seminoma, although gamma-gluramyl transpeptidase2 and human placental continued
• VOL 92/NO 1/JULY 1992/POSTGRADUATE MEDICINE
Postgraduate Medicine 1992.92:93-101.
Radical orchiectomy using a high inguinal approach is the initial treatment of testicular cancer.
alkaline phosphatase are showing some promise. 4'21 '22 A problem with the latter is its nearly universal elevation in smokers. 21 Also, Kuzmits and colleagues23 described the potential usefulness of serum neuron-specific enolase, which they demonstrated in seminoma cells. Lactate dehydrogenase is a nonspecific marker that may be useful in monitoring tumor bulk. 1,4,ll,ll Staging of disease Several staging systems for testicular cancer have been developed, u.s.7.17.l4-26 among them the international TNM system and the Indiana University system. The most commonly used is the A, B, C system or the corresponding I, II, III system (table 1). Stage B disease can be subdivided into B1, B2, and B3 on the basis of the number and/or size of retroperitoneal lymph nodes affected. 5·7·25 '26 Disease can also be categorized as early (stage I and early stage II) or advanced (advanced stage II and stage III). The size of retroperitoneal lymph nodes differentiates early from advanced stage II disease. 3 Staging (ie, determining the extent of disease) allows appropriate management and provides a baseline from which to evaluate therapeutic response. Useful studies are listed in table 2. 3·7
Table 1. Clinical stages of testicular cancer Stage
Extent of disease
A(l)
Confined to testis
B(ll)
Metastasis to retroperitoneal lymph nodes
C(lll)
Metastasis to supradiaphragmatic lymph nodes or involvement of visceral organs
Table 2. Appropriate tests for clinical evaluation to stage testicular cancer Laboratory tests Tumor markers (alpha fetoprotein, human chorionic gonadotropin) Lactate dehydrogenase (for monitoring tumor bulk) Uver function tests
Radiographic tests Chest films (posterior-anterior and lateral) Computed tomographic scan of chest if chest film is normal Computed tomographic scan of abdomen and pelvis
Lymphangiography and intravenous urography, once considered standard studies in staging evaluation, have essentially been replaced by computed tomography of the abdomen and pelvis. Although no radiographic method is totally reliable in determining the presence or absence of retroperitoneal lymph node involvement, computed
VOL 92/NO 1/JULY 1992/POSTGRADUATE MEDICINE • TUTICULAR CANCI!R
tomography is most often the method of choice.uA.ls
Treatment Radical orchiectomy using a high inguinal approach is the initial treatment of testicular cancer. A transscrotal approach to biopsy or orchiectomy is absolutely contraindicated because of the potential for local recurrence and continued
99
Chest films and testing for serum markers should be included at each office visit in patients treated for testicular cancer.
metastatic spread to the inguinal lymph nodes.3.4. 11 '17 Subsequent treatment is determined by histologic results and stage of disease.
Postgraduate Medicine 1992.92:93-101.
SEMINOMATOUS DISfAiiE-
Patients with early seminoma are treated with irradiation, because these tumors are exquisitely radiosensitive. Cure rates of95% to 97% for stage I and 85% to 90% for early stage II disease have been reported. 3'4 Most patients with advanced disease are treated with combination chemotherapy (described later). Treatment for partially regressed retroperitoneal disease is controversial. NONSEMINOMATOUS DISfAiiE-
Traditional treatment of stage I (or A) nonseminomatous disease is orchiectomy with retroperitoneal lymph node dissection. Cure rates of85% to 90% have been reported for microscopic disease.H Recently, orchiectomy alone with vigilant surveillance has been advocated in patients who meet strict criteria. This approach avoids surgical dissection in a large percentage of patients,3.4.27 but it is only for the motivated because follow-up is quite rigorous. If relapse occurs, chemotherapy can be instituted and has produced good success. Appropriate treatment of early stage II disease is controversial. Protocols include retroperitoneal lymph node dissection or
100
chemotherapy or a combination of both methods. For advanced stage II and stage III disease, initial treatment is combination chemotherapy. If a mass persists after chemotherapy and tumor markers are normal, surgical removal of the mass is necessary to ascertain whether it is malignant. Additional chemotherapy is indicated if cancer is found and is always required if tumor markers remain elevated. Tumor-reductive surgery should not be performed in these cases because it is rarely of benefit. 1.3.4.? Combination chemotherapy based on cisplatin (Platinol) has become standard treatment for disseminated testicular tumors. In the original study at the Indiana University School of Medicine, Indianapolis, 28 cisplatin was added to an already established regimen of vinblastine sulfate (Velban, Velsar) plus bleomycin sulfate (Blenoxane), forming the PVB regimen. Cisplatin has also been included in the various vinblastine and bleomycin protocols (VAB) studied at the Memorial Sloan-Kettering Cancer Center, New York. 1'7 Investigators at the Royal Marsden Hospital, Sutton, England29 administered etoposide (VePesid) in combination with cisplatin and bleomycin (BEP) and achieved results consistent
with those of the PVB and VAB regimens but with less morbidity. Williams and coworker~ 0 compared BEP with PVB therapy and also found diminished toxicity and, in patients with advanced disease, better efficacy with the BEP regimen. Both groups recommend BEP as firstline therapy. The use of these various agents combined with cisplatin achieves complete remission in 80% to 85% of patients.3'4 Ifosfamide (lfex) 331 and, occasionally, autologous bone marrow transplantation have been used for refractory disease. 3'4
Patient follow-up Follow-up must be meticulous. A thorough physical examination, posterior-anterior and lateral chest x-ray films, and appropriate serum marker testing should be included at each visit regardless of cell type or disease stage.3 Clinical stage I (A) patients with nonserninomatous disease who were treated with orchiectomy alone should have computed tomography of the abdomen and pelvis every 2 to 3 months for the first 2 years. 1
Summary Cure rates for testicular cancer have improved dramatically
naTICULAR CANCER • VOL 92/NO 1/JULY 1992/POSTGRAOUATE MEDICINE
Postgraduate Medicine 1992.92:93-101.
over the years, but early diagnosis is still essential. Primary care physicians have a responsibility to include testicular examination as part of cancer screening and to educate young male patients about the frequency of testicular cancer in their age-group and on how to perform self-examination. A high index of suspicion and careful bimanual palpation are crucial in evaluation of com-
plaints referable to the scrotum. Prompt urologic consultation must be obtained if a tu-
mor is suspected. IIUII
-®
Earn credit on this article. See CME Quiz.
Address for correspondence: H. Bruce Vogt, MD, 2501 W 22nd St, Sioux Falls, SO 57105.
References 1. Einhorn LH, Crawford ED, Shipley WU, et al. Cancer of the testes. In: DeVita Vf Jr,
Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 3d ed. Philadelphia: JB Lippincott, 1989:1071-98 2. Iammarino NK, Scardino PT. Testicular cancer: the role of the primary care physician in prevention and early detection. Tex Med 1991; 87(5):66-71 3. Gamick MB. Testicular cancer and other trophoblastic diseases. In: Wilson JO, Braunwald E, Isselbacher KJ, er al, eds. Harrison's principles of internal medicine. 12th ed. New York: McGraw-Hill, 1991:1625-9 4. Gamick MB. Testicular cancer. Semin Surg Oncoll989;5(4):22!-6 5. Loehrer PJ Sr, Wdliams SD, Einhorn LH. Testicular cancer: the quest continues. J Nad Cancerlnsr 1988;80(17): 1373-82 6. Boring CC, Squires TS, Tong T. Cancer statistics: 1991. CA 1991;41(1):19-36 [erratum, CA 1991;41(2):111] 7. Williams SD, Einhorn l.H. Neoplasms of the testis. In: Calabresi P, Schein PS, Rosenberg SA, eds. Medical oncology: basic principles and clinical management of cancer. New York: Macmillan, 1985:1077-88 8. Schottenfdd D, Warshauer ME. Testis. In: Schonenfeld 0, Fraumeni JF Jr, eds. Cancer epidemiology and prevention. Philadelphia: WB
Saunders, 1982:947-57 9. Hawtrey CE. Undescended testis and orchiopexy: recent observations. Pediarr Rev 1990; II (I 0):305-8 10. Giwercman A, Bruun E, Frimodt-Meller C, et al. Prevalence of carcinoma in situ and other histopathological abnormalities in testes of men with a history of cryptorchidism. J Ural 1989; 142(4):998-1 002 11. Owls RF, Williams SD. Testicular cancer. Curr Probl Cancer 1989;13(5):285-335 12. GoedertJJ, McKeen EA,Javadpour N, et al. Polythelia and testicular cancer. Ann Intern Med 1984;101(5):646-7 13. WrightJC. Upclare in cancer chemotherapy: genitourinary tract cancer. 4. Testicular cancer. J Nad Med Assoc 1988;80(4):425-35 [errata, J Nad Med Assoc 1988;80(6):6!6 and 1988;80(8):following 840] 14. Dilwonh JP, Farrow GM, Oesterling JE. Non-germ cell rumors of testis. Urology 1991; 37(5):399-417 15. US PrevmiM Services Task Force. Guide to clinical preventive services: an assessment of the effectiveness of 169 interventions. Baltimore: Williams & Wilkins, 1989 16. Bosl GJ, Vogdzang NJ, Goldman A, et al. Impact of delay in diagnosis on clinical stage of testicular cancer. Lancer 1981 ;2(8253):970-3 17. Richie JP. Testicular cancer. Compr Ther
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1990;16(11):11-4 18. Selman SH, Mayhew HE, Heth WL. Urinary traer disorders. In: Rake! RE, ed. Textbook of family practice. 4th ed. Philadelphia: WB Saunders, 1990: 1349-97 19. TscngAJr, HomingSJ, FrcihaFS, et al. Gynecomastia in testicular cancer patients: prognostic and therapeutic implications. Cancer 1985;56(1 0):2534-8 20. Rowland RG, Donohue JP. Testicular cancer: innovations in diagnosis and rrcarment. Semin Urol!988;6(3):223-32 21. Rowland RG. Serum markers in testicular germ-cell neoplasms. Hematol Oneal Clin North Am 1988;2(3):485-9 22. Lightner DJ, Lange PH. Testicular rumors. lmmunol Series 1990;53:397-40! 23. Kuzmits R, Schcmthaner G, Krisch K. Serum neuron-specific enolase: a marker for response to therapy in seminoma. Cancer 1987; 60(5):1017-21 24. Birch R, Wdliams S, Cone A, et a1. Prognostic factors for favorable outcome in disseminated germ cell rumors. J Clin Oneal 1986; 4(3):400-7 25. Smith RB, Haskell CM. Testis. In: Haskell CM, ed. Cancer treatment. 3d ed. Philadelphia: WB Saunders, 1990:779-97 26. Einhorn LH, Lowitt BB, Casciato DA. Testicular cancer. In: Casciato DA, Lowirz BB, eds. Manual of clinical oncology. 2d ed. Boston: Little, Brown, 1988: 189-97 27. Hesketh PJ, Krane RJ. Prognostic assessment in nonseminomatous testicular cancer: implications for therapy. J Ural 1990; 144( I): 1-9 28. Einhorn LH, Donohue}. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 1977;87(3): 293-8 29. Peckham MJ, Barrett A, Lic:w KH, et a1. The treatment of metastatic germ-cell testicular rumours with bleomycin, etoposide and cisplarin (BEP). Br J Cancer 1983;47(5):6!3-9 30. Wdliams SD, Birch R, Einhorn LH, et al. Treatment of disseminated germ-cell rumors with cisplarin, bleomycin, and either vinblastine or etoposide. N EnglJ Med 1987;316(23): 1435-40 31. Whccler BM, Loehrer PJ, Wdliams SD, et al. Ifosfamide in refractory male germ cell rumors. J Clin Oncol!986;4(1):28-34
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ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Testicular cancer H. Bruce Vogt MD & Michael S. McHale MD To cite this article: H. Bruce Vogt MD & Michael S. McHale MD (1992) Testicular cancer, Postgraduate Medicine, 92:1, 93-101, DOI: 10.1080/00325481.1992.11701393 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701393
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [RMIT University Library]
Date: 15 June 2016, At: 18:47
Symposium
Second of four articles on urologic problems
(and much larger) between ages 20 and 35. Malignant testicular neoplasms are rare after age 40, and if found in a patient over age Role of primary care physicians in screening 50, lymphoma should be susand education pected. Although the incidence of testicular cancer is increasing, 2'7 monality rates are improving because of successful treatment. In 1977, this disease was the third leading cause of cancer death in men aged 15 to 34; today, it is Preview not among the top five causes.3.4.6 The typical attitude of the young is that serious disease is The major predisposing factor for older folks. However, this is clearly untrue in the case of to development of testicular cantesticular cancer, which largely affects teenagers and young cer is cryptorchidism, which conadults. Since its only sign may be a painless mass, physical fers a risk 2.5 to 40 times that examination by physicians and by the patients themselves is found in the general population. 8 of utmost importance. The authors summarize screening for the disease and treatment methods, which are chosen on the The incidence of malignant transformation in these patients basis of the stage of disease. has been reponed as ranging from 3% to 18% (mean, 11 %) .9 Giwercman and associates 10 conerative techniques, and highly H. Bruce Vogt, MD cluded from their studies and effective systemic chemotheraMichael S. McHale, MD other Scandinavian studies that peutic agents. 3· 5 The major role the true incidence is between 2% of primary care physicians in •) Although it is a relatively rare and3%. management of testicular cancer disease, testicular cancer is the The risk is panicularly high in is in educating young men on most common type of cancer in 12 patients with an intra-abdominal the dangers of the disease and on men aged 15 to 35. ' Dramatic how to perform self-examination. testis. 11 Although cancer usually advances in its treatment have develops in the undescended made testicular cancer a model testis, in 15% to 20% of cases it Predisposing factors for curable, solid, malignant occurs in the contralateral, norAbout 6, 100 new cases of testicuneoplasms. These advances inmally positioned testis, which lar cancer/ or 4 per 100,000 popcluded the development of radiosuggests an underlying testicular ulation/ are reponed annually in immunoassays for sensitive tu78 defect. Whether orchiopexy at a • United States. The disease the mor markers and an integrated young age reduces subsequent has two peaks in frequency: one approach to management comnot been established, but risk has in early childhood and another bining irradiation, improved op-
Postgraduate Medicine 1992.92:93-101.
Testicular cancer
continued
VOL 92/NO 1/JULY 1992/POSTGRADUATE MEDICINE • 'RSTICULAR CANCER
93
Postgraduate Medicine 1992.92:93-101.
The vast majority of primary testicular tumors are of germ cell origin and are malignant.
rhe procedure should be completed ro allow careful follow-up of patients with cryptorchidism. Intra-abdominal testes should be removed. 2 Additional risk factors include previous cancer in the opposite testis, a history of mumps orchitis, inguinal hernia or hydrocele in childhood, family history of cryptorchidism, white race, and a high socioeconomic srarus. 2·4An increased prevalence is also seen in patients with gonadal dysgenesis and in those with Klinefelter's syndrome (ie, XXY chromosome complement). 8 In one study, 12 rhe presence of supernumerary nipples was associated with an increased incidence. However, in most patients, no predisposing factor can be implicared.3·4
Classification of disease The vast majority (96%) of primary testicular rumors are of germ cell origin and are malignant.1'13 There are four classic cell types, which can be divided into five pathologic entities according to the Dixon and Moore classification: seminoma, embryonal carcinoma, teratoma (adult), choriocarcinoma, and teratocarcinoma (teratoma with embryonal carcinoma). Pure seminoma accounts for 40% of testicular cancers. 1'13 Seminona can be subclassified
94
as classic (or typical), anaplastic, or spermatocyric. 1'7 The spermatocyric type occurs in older patients, is the most common germ cell rumor after age 70, and has the highest incidence ofbilarerality.11 Embryonal carcinoma (which includes yolk sac or endodermal sinus rumors in some classification systems) accounts for 1So/o ro 20% of testicular cancers.w This is a very aggressive rumor, and many patients have metastatic disease when diagnosed. 11 Embryonal carcinoma is more common in infants and young children bur is more aggressive when seen in adults. 1 Teratomas contain elements from two or more of the germinal celllayers. 3·7 They are less aggressive than other nonseminomatous rumors bur do have merastatic potential. When mitotic figures are identified within the rumor, the teratoma is referred to as immature. 1 Choriocarcinoma, which accounts for 1o/o of testicular rumors, is the most malignant type. 13 Syncyriorrophoblasric cells must be identified histologically ro establish irs diagnosis. These cells are responsible for the secretion of human chorionic gonadotropin (hCG), an important rumor marker. 1 Non-germ cell rumors account for about So/o of testicular
cancers. 14 Of these, rete cord or gonadal stromal types predominate and include rumors of Leydig, Serroli, granulosa, theca, and mixed cell origin. Several malignant neoplasms have been described as metastasizing ro the testis. Perhaps rhe most important is lymphoma, because ir is nor unusual; ir represents So/o of all testicular rumors.14 Whether primary lymphoma can develop in the testis is controversial. The median age of these patients is 60, and 80% of them are over age 50. 14 The critical distinction for clinicians is whether a rumor is a seminomarous or nonseminomatous germ cell neoplasm. Patient screening Primary care physicians should include examination of the testes in their cancer screening activities. The US Preventive Services Task Force 15 specifically recommends screening in males with a history of cryptorchidism, orchiopexy, or testicular atrophy. The task force makes no recommendation for or against screening in males who are nor ar high risk, bur testicular examination should be performed during any screening physical if iris nor part of a planned preventive program. As noted, in most patients with cancer of the testis, no predisposing factor is identified. 3·4
TUTICULAR CANCIUI • VOL 92/NO 1/JULY 1992/POSTGRAOUATE MEDICINE
Postgraduate Medicine 1992.92:93-101.
Physical examinations for high school athletics and college entrance are excellent opportunities to educate young men on testicular self-examination.
Primary care physicians should take advantage of the office visit for a physical examination to provide patient education and promote testicular self-examination. Examples of excellent opportunities for such education include physical examinations for high school athletics and college entrance. Many young men are unaware of the existence of testicular cancer in their age-group. 16 Patients should be taught the technique of testicular self-examination2'3 and given a handout to reinforce the information. Among the useful available pamphlets are Testicular Self-Examination, published by the National Cancer Institute, and For Men Only. published by the American Cancer Society. To encourage early self-referral, physicians should stress as pan of their patient education the excellent prognosis associated with early treatment of testicular cancer. Although most patients have a favorable outcome, a poorer prognosis is seen with advanced disease, and there is a clear correlation between the interval from onset of symptoms to diagnosis and the stage of disease. 16
Clinical presentation The most common manifestation of testicular cancer is a painless mass.u' 13 '17 '18 The spectrum of complaints, however, is broad.
H. Bruce Vogt, MD Dr Vogt is professor of family medicine and dean of graduate medical education, University of South Dakota School of Medicine, Sioux Falls.
Some patients do have pain. Others report a heavy sensation in the scrotum1'2 or swelling or a change in the consistency of the testis. 24 Acute pain may be secondary to torsion or epididymitis3'4 or caused by intratesticular bleeding1or infarction. 11 Patients with advanced disease may present with weight loss, abdominal or back pain secondary to retroperitoneal adenopathy, or dyspnea from pulmonary metastases. 24 Gynecomastia may result from increased hCG levels. 24· 11 In a small study, Tseng and colleagues19 reported a 10% inci-
dence of gynecomastia or severe breast tenderness in association with elevated hCG. Other presenting symptoms or signs include infertility11 and, in advanced disease, supraclavicular adenopathy and urinary obstruction. 3'4
Diagnostic evaluation Differential diagnosis of a scrotal mass includes epididymitis, inguinal hernia, hydrocele, spermatocele, and testicular torsion. 2 Pain, fever, leukocytosis, and pyuria usually accompany epididymitis, and abrupt onset of severe pain is the hallmark of tor-
continued
VOL 92/NO 1/JULY 1992/POSTGRADUATE MEDICINE • 'RSTICULAR CANCER
95
The tumor markers alpha fetoprotein and human chorionic gonadotropin are most useful for early determination of relapse in patients treated for testicular cancer.
my with pathologic examination. Before surgery, blood should be obtained for subsequent determinations of tumor markers if cancer is diagnosed.3.4
Postgraduate Medicine 1992.92:93-101.
Michael S. McHale, MD Dr McHale is a hematologistoncologist in private practice in Omaha.
sion. 2'18 Hydroceles and spermatoceles are painless, transilluminable masses. Primary care physicians should maintain a high index of suspicion when evaluating a scrotal mass. Abnormalities are best diagnosed by careful bimanual palpation. 11 Occasionally, a lesion of the testis may be indistinguishable from one of the epididymis. 18 Bilateral transscrotal ultrasonography can be of assistance in such cases,3•4•17'20 as well as when no palpable mass or only a minimally definable lesion is present.
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A definite testicular mass must be considered malignant until proven otherwise, and the patient should be promptly referred to a urologist. 18 In their study, Einhorn and associates1 found that 55% of patients eventually found to have cancer were initially treated for epididymitis. Unfortunately, because of physician and patient delays, a 3- to 6-month period between initial symptom and diagnosis is common.7 Definitive diagnosis of testicular cancer is made by orchiecto-
TESncUL.AR
~R
Tumor markers Alpha fetoprotein and hCG are biologic tumor markers that are routinely used in the management of testicular cancer. 1'3'21 They can detect early or smallvolume disease but are most useful for early determination of relapse in previously treated patients.21 Alpha fetoprotein is a glycoprotein produced by cells of fetal origin. An increase in patients with pure seminoma has never been documented. Therefore, if it is detected, the patient must be treated as having nonseminomatous disease, regardless of the pathology. IJ.I? Alpha fetoprotein is commonly detected in embryonal carcinoma. 3 A glycoprotein produced by syncytiotrophoblasts,3'21 hCG is most often found in choriocarcinoma. However, it can be detected in embryonal carcinoma3 and in about 10% of cases of seminoma. 1It may stimulate testicular secretion of estrogen, resulting in gynecomastia. 3 No useful clinical marker has been found for seminoma, although gamma-gluramyl transpeptidase2 and human placental continued
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Radical orchiectomy using a high inguinal approach is the initial treatment of testicular cancer.
alkaline phosphatase are showing some promise. 4'21 '22 A problem with the latter is its nearly universal elevation in smokers. 21 Also, Kuzmits and colleagues23 described the potential usefulness of serum neuron-specific enolase, which they demonstrated in seminoma cells. Lactate dehydrogenase is a nonspecific marker that may be useful in monitoring tumor bulk. 1,4,ll,ll Staging of disease Several staging systems for testicular cancer have been developed, u.s.7.17.l4-26 among them the international TNM system and the Indiana University system. The most commonly used is the A, B, C system or the corresponding I, II, III system (table 1). Stage B disease can be subdivided into B1, B2, and B3 on the basis of the number and/or size of retroperitoneal lymph nodes affected. 5·7·25 '26 Disease can also be categorized as early (stage I and early stage II) or advanced (advanced stage II and stage III). The size of retroperitoneal lymph nodes differentiates early from advanced stage II disease. 3 Staging (ie, determining the extent of disease) allows appropriate management and provides a baseline from which to evaluate therapeutic response. Useful studies are listed in table 2. 3·7
Table 1. Clinical stages of testicular cancer Stage
Extent of disease
A(l)
Confined to testis
B(ll)
Metastasis to retroperitoneal lymph nodes
C(lll)
Metastasis to supradiaphragmatic lymph nodes or involvement of visceral organs
Table 2. Appropriate tests for clinical evaluation to stage testicular cancer Laboratory tests Tumor markers (alpha fetoprotein, human chorionic gonadotropin) Lactate dehydrogenase (for monitoring tumor bulk) Uver function tests
Radiographic tests Chest films (posterior-anterior and lateral) Computed tomographic scan of chest if chest film is normal Computed tomographic scan of abdomen and pelvis
Lymphangiography and intravenous urography, once considered standard studies in staging evaluation, have essentially been replaced by computed tomography of the abdomen and pelvis. Although no radiographic method is totally reliable in determining the presence or absence of retroperitoneal lymph node involvement, computed
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tomography is most often the method of choice.uA.ls
Treatment Radical orchiectomy using a high inguinal approach is the initial treatment of testicular cancer. A transscrotal approach to biopsy or orchiectomy is absolutely contraindicated because of the potential for local recurrence and continued
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Chest films and testing for serum markers should be included at each office visit in patients treated for testicular cancer.
metastatic spread to the inguinal lymph nodes.3.4. 11 '17 Subsequent treatment is determined by histologic results and stage of disease.
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SEMINOMATOUS DISfAiiE-
Patients with early seminoma are treated with irradiation, because these tumors are exquisitely radiosensitive. Cure rates of95% to 97% for stage I and 85% to 90% for early stage II disease have been reported. 3'4 Most patients with advanced disease are treated with combination chemotherapy (described later). Treatment for partially regressed retroperitoneal disease is controversial. NONSEMINOMATOUS DISfAiiE-
Traditional treatment of stage I (or A) nonseminomatous disease is orchiectomy with retroperitoneal lymph node dissection. Cure rates of85% to 90% have been reported for microscopic disease.H Recently, orchiectomy alone with vigilant surveillance has been advocated in patients who meet strict criteria. This approach avoids surgical dissection in a large percentage of patients,3.4.27 but it is only for the motivated because follow-up is quite rigorous. If relapse occurs, chemotherapy can be instituted and has produced good success. Appropriate treatment of early stage II disease is controversial. Protocols include retroperitoneal lymph node dissection or
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chemotherapy or a combination of both methods. For advanced stage II and stage III disease, initial treatment is combination chemotherapy. If a mass persists after chemotherapy and tumor markers are normal, surgical removal of the mass is necessary to ascertain whether it is malignant. Additional chemotherapy is indicated if cancer is found and is always required if tumor markers remain elevated. Tumor-reductive surgery should not be performed in these cases because it is rarely of benefit. 1.3.4.? Combination chemotherapy based on cisplatin (Platinol) has become standard treatment for disseminated testicular tumors. In the original study at the Indiana University School of Medicine, Indianapolis, 28 cisplatin was added to an already established regimen of vinblastine sulfate (Velban, Velsar) plus bleomycin sulfate (Blenoxane), forming the PVB regimen. Cisplatin has also been included in the various vinblastine and bleomycin protocols (VAB) studied at the Memorial Sloan-Kettering Cancer Center, New York. 1'7 Investigators at the Royal Marsden Hospital, Sutton, England29 administered etoposide (VePesid) in combination with cisplatin and bleomycin (BEP) and achieved results consistent
with those of the PVB and VAB regimens but with less morbidity. Williams and coworker~ 0 compared BEP with PVB therapy and also found diminished toxicity and, in patients with advanced disease, better efficacy with the BEP regimen. Both groups recommend BEP as firstline therapy. The use of these various agents combined with cisplatin achieves complete remission in 80% to 85% of patients.3'4 Ifosfamide (lfex) 331 and, occasionally, autologous bone marrow transplantation have been used for refractory disease. 3'4
Patient follow-up Follow-up must be meticulous. A thorough physical examination, posterior-anterior and lateral chest x-ray films, and appropriate serum marker testing should be included at each visit regardless of cell type or disease stage.3 Clinical stage I (A) patients with nonserninomatous disease who were treated with orchiectomy alone should have computed tomography of the abdomen and pelvis every 2 to 3 months for the first 2 years. 1
Summary Cure rates for testicular cancer have improved dramatically
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over the years, but early diagnosis is still essential. Primary care physicians have a responsibility to include testicular examination as part of cancer screening and to educate young male patients about the frequency of testicular cancer in their age-group and on how to perform self-examination. A high index of suspicion and careful bimanual palpation are crucial in evaluation of com-
plaints referable to the scrotum. Prompt urologic consultation must be obtained if a tu-
mor is suspected. IIUII
-®
Earn credit on this article. See CME Quiz.
Address for correspondence: H. Bruce Vogt, MD, 2501 W 22nd St, Sioux Falls, SO 57105.
References 1. Einhorn LH, Crawford ED, Shipley WU, et al. Cancer of the testes. In: DeVita Vf Jr,
Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 3d ed. Philadelphia: JB Lippincott, 1989:1071-98 2. Iammarino NK, Scardino PT. Testicular cancer: the role of the primary care physician in prevention and early detection. Tex Med 1991; 87(5):66-71 3. Gamick MB. Testicular cancer and other trophoblastic diseases. In: Wilson JO, Braunwald E, Isselbacher KJ, er al, eds. Harrison's principles of internal medicine. 12th ed. New York: McGraw-Hill, 1991:1625-9 4. Gamick MB. Testicular cancer. Semin Surg Oncoll989;5(4):22!-6 5. Loehrer PJ Sr, Wdliams SD, Einhorn LH. Testicular cancer: the quest continues. J Nad Cancerlnsr 1988;80(17): 1373-82 6. Boring CC, Squires TS, Tong T. Cancer statistics: 1991. CA 1991;41(1):19-36 [erratum, CA 1991;41(2):111] 7. Williams SD, Einhorn l.H. Neoplasms of the testis. In: Calabresi P, Schein PS, Rosenberg SA, eds. Medical oncology: basic principles and clinical management of cancer. New York: Macmillan, 1985:1077-88 8. Schottenfdd D, Warshauer ME. Testis. In: Schonenfeld 0, Fraumeni JF Jr, eds. Cancer epidemiology and prevention. Philadelphia: WB
Saunders, 1982:947-57 9. Hawtrey CE. Undescended testis and orchiopexy: recent observations. Pediarr Rev 1990; II (I 0):305-8 10. Giwercman A, Bruun E, Frimodt-Meller C, et al. Prevalence of carcinoma in situ and other histopathological abnormalities in testes of men with a history of cryptorchidism. J Ural 1989; 142(4):998-1 002 11. Owls RF, Williams SD. Testicular cancer. Curr Probl Cancer 1989;13(5):285-335 12. GoedertJJ, McKeen EA,Javadpour N, et al. Polythelia and testicular cancer. Ann Intern Med 1984;101(5):646-7 13. WrightJC. Upclare in cancer chemotherapy: genitourinary tract cancer. 4. Testicular cancer. J Nad Med Assoc 1988;80(4):425-35 [errata, J Nad Med Assoc 1988;80(6):6!6 and 1988;80(8):following 840] 14. Dilwonh JP, Farrow GM, Oesterling JE. Non-germ cell rumors of testis. Urology 1991; 37(5):399-417 15. US PrevmiM Services Task Force. Guide to clinical preventive services: an assessment of the effectiveness of 169 interventions. Baltimore: Williams & Wilkins, 1989 16. Bosl GJ, Vogdzang NJ, Goldman A, et al. Impact of delay in diagnosis on clinical stage of testicular cancer. Lancer 1981 ;2(8253):970-3 17. Richie JP. Testicular cancer. Compr Ther
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1990;16(11):11-4 18. Selman SH, Mayhew HE, Heth WL. Urinary traer disorders. In: Rake! RE, ed. Textbook of family practice. 4th ed. Philadelphia: WB Saunders, 1990: 1349-97 19. TscngAJr, HomingSJ, FrcihaFS, et al. Gynecomastia in testicular cancer patients: prognostic and therapeutic implications. Cancer 1985;56(1 0):2534-8 20. Rowland RG, Donohue JP. Testicular cancer: innovations in diagnosis and rrcarment. Semin Urol!988;6(3):223-32 21. Rowland RG. Serum markers in testicular germ-cell neoplasms. Hematol Oneal Clin North Am 1988;2(3):485-9 22. Lightner DJ, Lange PH. Testicular rumors. lmmunol Series 1990;53:397-40! 23. Kuzmits R, Schcmthaner G, Krisch K. Serum neuron-specific enolase: a marker for response to therapy in seminoma. Cancer 1987; 60(5):1017-21 24. Birch R, Wdliams S, Cone A, et a1. Prognostic factors for favorable outcome in disseminated germ cell rumors. J Clin Oneal 1986; 4(3):400-7 25. Smith RB, Haskell CM. Testis. In: Haskell CM, ed. Cancer treatment. 3d ed. Philadelphia: WB Saunders, 1990:779-97 26. Einhorn LH, Lowitt BB, Casciato DA. Testicular cancer. In: Casciato DA, Lowirz BB, eds. Manual of clinical oncology. 2d ed. Boston: Little, Brown, 1988: 189-97 27. Hesketh PJ, Krane RJ. Prognostic assessment in nonseminomatous testicular cancer: implications for therapy. J Ural 1990; 144( I): 1-9 28. Einhorn LH, Donohue}. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 1977;87(3): 293-8 29. Peckham MJ, Barrett A, Lic:w KH, et a1. The treatment of metastatic germ-cell testicular rumours with bleomycin, etoposide and cisplarin (BEP). Br J Cancer 1983;47(5):6!3-9 30. Wdliams SD, Birch R, Einhorn LH, et al. Treatment of disseminated germ-cell rumors with cisplarin, bleomycin, and either vinblastine or etoposide. N EnglJ Med 1987;316(23): 1435-40 31. Whccler BM, Loehrer PJ, Wdliams SD, et al. Ifosfamide in refractory male germ cell rumors. J Clin Oncol!986;4(1):28-34
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