Testicular cancer in blacks. A multicenter experience

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Testicular Cancer in Blacks A Multicenter Experience Judd W. M o d , M.D.,*,t Francis J. Schanne, B.S.,*,t lan M . Thompson, M.D.,$ Harold A. Frazier, M.D.,t§ Samuel A . Peretsman, M.D., (1 John N . Wefflaufer,M.D.,lT Thomas A . Rozanski, M.D.,# Richard S. Stack, M.D.,** Karl J. Kreder, M.D.,** and Kenneth J. Hoffman, M.D., Ph.D.tt

Background. The rarity of testis tumor in black patients has made the study of a large series difficult. Much of the epidemiologic and clinical information regarding this neoplasm in this population is in dispute, including data on incidence, prognosis, histologic distribution, age and stage at presentation, and side distribution. Methods. A retrospective review of 66 blacks with testicular tumors from seven military medical centers was performed. Results. Similar results were found for blacks with testis tumor to those of the general testis cancer population regarding prognosis, side distribution, and age of onset for nonseminoma and interstitial tumors. There is a slight increase in the expected number of interstitial tumors in blacks, but the distribution between seminoma and nonseminoma is similar to the general population. The mean age of presentation for seminoma in blacks was younger than that of the general testis cancer population. For testis tumor treated at the same institution, there was an increased delay of diagnosis in blacks compared with whites. The number of new cases of testicular From the Urology Services at 'Walter Reed Army Medical Center, Washington, DC; $Brooke Army Medical Center, San Antonio, Texas; GNational Naval Medical Center, Bethesda, Maryland; IlWilford Hall United States Air Force Medical Center, San Antonio, Texas; (Madigan Army Medical Center, Tacoma, Washington; #Tripler Army Medical Center, Honolulu, Hawaii; and **Fitzsimons Army Medical Center, Aurora, Colorado; and from the Departments of tSurgery and ttPreventive Medicine and Biornetrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Supported by the Uniformed Services University of the Health Sciences Intramural Grant no. R090BJ and the Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC. The authors thank Ms. Michelle Dixon for typing and editing the manuscript. Address for reprints: Judd W. Moul, M.D., Department of Surgery, USUHS,4301 Jones Bridge Road, Bethesda, MD 20814-4799. The opinions and assertions contained herein are the private views of the authors and should not be construed as reflecting the views of the Department of Defense or the United States Army, Navy, or Air Force. Accepted for publication August 18, 1993.

cancer between 1979 and 1991 at one major center was increased for whites but not for blacks. The availability of cisplatin-based combination chemotherapy has resulted in an improved prognosis for blacks, as has already been demonstrated for white populations. Conclusions. Testis tumor in blacks behaves similarly to testis tumor in the general population except that in blacks there are more interstitial tumors and the mean age of presentation for seminoma is younger. Further, there is an increased delay in diagnosis for blacks compared with whites, but the incidence of this tumor in this population does not appear to be increasing. Cisplatinbased chemotherapy has significantly improved survival in this population. Cancer 1994;73:388-93. Key words: testicular, cancer, black race, seminoma, nonseminoma.

The rarity and limited experience with testis tumor in black patients is well known, which has made the study of a large series difficult.'-22 Because of this, certain clinical information regarding this neoplasm in this population is in dispute. Although early reports suggested that blacks with testicular cancer had a worse prognosis because of a higher percentage of patients with nonsemi no ma^,',^ later reports suggested a better prognosis due to a higher proportion of blacks with seminoma." Yet other investigators found an equal prognosis between whites and b l a ~ k s . ~ , 'Some ~ , ' ~ have implicated that delay in diagnosis has been more pronounced in blacks, leading to more advanced stage and potentially worse survival time."-I3 Regarding age, studies have suggested blacks with testis cancer tend to be older?'' or the same age9,I5as their white counterparts. The side distribution of tumors is even disputed. Some reports have noted a higher incidence of rightsided tumors in whereas other reports noted more left-sided inv~lvement.'"~The most recent controversy involves whether testicular cancer is increasing

Testicular Cancer in Blacks/Moul et al. in blacks as has been seen in the white population. One report suggested that testis cancer was increasing in blacks,I4however, that was refuted by recent Surveillance, Epidemiology, and End Results program of the National Cancer Institute data." Military medical centers care for a disproportionate number of young black males compared with most civilian centers. By collecting data from multiple military medical centers over several decades, we have been able to develop one of the largest series of black patients with testicular tumors to date. In the current study, we analyzed this patient group retrospectively to determine statistical trends in many clinical aspects of testicular cancer and compared these findings with previously published results. Additionally, we have established a large retrospective series of white patients treated for testicular cancer at Walter Reed Army Medical Center over the same time period for the comparison of white and black patients treated for testicular cancer at the same institution. Methods and Materials

The records of 66 blacks with testicular cancer from seven centers from 1947 through 1991 were reviewed: 20 patients from Walter Reed Army Medical Center seen from 1979 to 1991 (to update a previous report);" 12 from Brooke Army Medical Center (1947-1991); 11 from Wilford Hall Medical Center (1965-1991); 8 from National Naval Medical Center (1970-1991); and 5 each from Fitzsimmons Army Medical Center (19651989), Madigan Army Medical Center (1970-1991), and Tripler Army Medical Center (1949-1991). A data base sheet was constructed by several of us (J.W.M., F.J.S.,K.J.H.)and distributed to participating investigators (I.M.T., H.A.F., S.A.P., J.N.W., T.A.R., R.S.S., K.J.K.),who extracted the data from inpatient and outpatient records. Completed data sheets were returned to one of us and reviewed (J.W.M.). A computer data base was created (F.J.S.,K.J.H.)and data was entered by one of us (F.J.S.). The data base was developed and initial frequency and cross-tabulation was done by using Epi. Info. computer software (Centers for Disease Control, Atlanta, GA).23The data of these patients was reviewed for trends in demographics, histology, side distribution, age at presentation, signs and symptoms at presentation, delay in diagnosis, stage at presentation, mean duration of follow-up, and survivorship. A lifetime analysis was done to assess the probability of death from the time of initial diagnosis of testicular cancer.24Subanalysis of the incidence of black testis tumor, delay in diagnosis, and the frequency of testicular self-exam relative to whites was accomplished by comparing data from these 66 black patients from the

389

data of 302 white patients treated at Walter Reed Army Medical Center from 1979 to 1991. Pathology was classified as proposed by Dixon and Moore.25 Clinical pathologic staging was as follows: Stage I, disease confined to the testicle; Stage IIA, fewer than or equal to six microscopically positive retroperitoneal nodes or nodal disease measuring less than 2 cm in diameter; Stage IIB, more than six microscopic nodes or nodal disease measuring greater than 2 cm; and Stage 111, metastatic disease above the diaphragm or visceral organ metastases. Results

Figure 1 shows the distribution of patients from seven military medical centers including the total number of patients with testicular tumors seen during the data collection period, the number of black patients diagnosed at that center, and the percentage of patients with testicular cancer who were black. Overall, 2285 patients with testicular cancer were reviewed, and 66 (2.9%) of those patients were black (range, 1.9-5.1%). Table 1 shows the number of patients with testicular cancer treated at Walter Reed Army Medical Center divided by race. From 1979 to 1981, blacks composed 5.1% (3 of 59) of cases. They composed 9.6% (7 of 73) from 1982 to 1984, 5.7% (5 of 87) from 1985 to 1987, and 5.0% (5 of 120) from 1988 to 1991. The racial distribution shows no trend in either direction. The histologic composition of this series was 33 (50%) nonseminoma, 29 (43.9%) seminoma, and 4 (6.1%) interstitial (three Leydig and one Sertoli). There was equal side distribution, with 31 right-sided, 34 leftsided, and one abdominal tumor. Four of 63 evaluable patients (6.3%) had a history of undescended testicle. The mean age for the entire cohort was 28 years: for nonseminoma, 24.5 years; for seminoma, 30 years; and for interstitial tumors, 42 years. Regarding testicular tumor signs and symptoms, 56% (35 of 62) of patients experienced pain, with 27 patients noting testicular pain and 5 having abdominal pain. Forty-five of 61 (74%) patients demonstrated a mass including one hydrocele and one abdominal mass. Only 6.7% (4 of 60) of black patients palpated a testicular mass on selfexamination, compared with 27 of 240 (11.25%)evaluable white patients (Walter Reed Army Medical Center). Delay in diagnosis was measured from the time of initial onset of symptoms until pathologic diagnosis at the time of orchiectomy. The mean delay in diagnosis for nonseminoma patients was 11.5 weeks; for seminoma patients, 20.3 weeks; for interstitial tumors, 23 weeks; and overall, 15.5 weeks. For 11 evaluable blacks treated at Walter Reed Army Medical Center, the delay

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2a 20

5

.........

..........

15

. . . . . . . . . . .........

1 2

10

5

0-

WRAMCBAMC WHMC 30509-91)

346(4741)

597(65.91)

Figure 1. The number of black patients with testicular cancer from each institution (black bars) and the 8 percentage of black patients with testicular cancer among each hospital testicular cancer population (gray bars). Bottom line provides total 5 5 number of testicular cancers and years of review for each institution. WRAMC: Walter Reed Army Medical Center; BAMC: Brooke Army Medical Center; WHMC: Wilford Hall Air Force Medical Center; MAMC: Madigan Army Medical Center; TAMC: Tripler Army Medical Center; FAMC: Fitzsimons Army NNMC MAMC TAMC FAMC 345VOQ1) 181WSI) 222(49-91) 223(a-8Q) Medical Center. ............

LL

in diagnosis was 20.4 weeks, whereas the delay in diagnosis for 196 evaluable white patients seen at Walter Reed Army Medical Center during a similar time period was 16.7 weeks. For patients diagnosed with epididymitis and treated with antibiotics before a tumor was diagnosed correctly, the mean delay was 14.4 weeks and for all others the delay was 16 weeks. Regarding stage, 22 of 29 (75.9%)of seminoma was seen initially as Stage I, and the remaining 24.1% (7 of 29) was seen initially as Stage I1 (6 as IIA, 1 as IIB). For nonseminoma, 8 (24%),4 (12%), 13 (40%),and 8 (24%) of 33 patients were seen initially as Stages I, IIA, IIB, and 111, respectively. Therefore, although 63.6% (21 of 33) of nonseminoma was seen initially as late stage (IIb or 111), only 3.4% (1 of 29) of seminoma was seen initially as late stage. Table 1. New Cases of Testicular Cancer Diagnosed at Walter Reed Army Medical Center (Washington,D. C.) per Year, Sorted by Ethnic Group Ethnic group Whites Blacks Other Total

1979-1981

1982-1984

~

. . . . . . . . . . ..........

1985-1987

1988-1991

_________

N (Oh)

N (Yo)

N (Oh)

N (Oh)

52 (88.1) 3 (5.1) 4 (6.8) 59

64 (87.7) 7 (9.6) 2 (2.7) 73

78 (89.7) 5 (5.7) 6 (4.6) 87

108 (90) 6 (5) 6 (5)

120

For seminoma, 25 evaluable patients were followed a mean of 108 months (range, 2-290 months), with 23 (92%) being alive with no evidence of disease, 1 being alive with cancer, and 1having died of other causes. No cancer-specific deaths occurred in the seminoma or interstitial tumor groups. At a mean follow-up of 55 months (range, 2-154 months) for 33 nonseminoma patients, 20 (63.3%)were alive with no evidence of disease, 2 were alive with cancer, 7 (23.3%)died of testicular cancer, 2 (6.6%)died of other causes, and 2 were lost to follow-up. A life table survivorship graph for patients treated before 1980 (when combination cisplatin chemotherapy began to gain widespread use) is illustrated in Figure 2. A life table survivorship graph for nonseminoma patients treated after 1980 is illustrated in Figure 3. For 8 patients treated before 1980, there were 3 cancer deaths and survivorship was 62%, whereas for 23 patients treated after 1980, there were 4 deaths and survivorship was 78%, illustrating an effect of effective combination chemotherapy in this population. Discussion

The most important finding of this study is that the behavior of testicular cancer in black patients appears virtually identical to the behavior of this neoplasm in the white population. Aside from a higher incidence of

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Testicular Cancer in BlackslMoul et al.

% SURVIVORSHIP

Figure 2. Life table survival graph for black patients with nonseminoma treated before the widespread use of cisplatin-combination chemotherapy in 1980. For the eight evaluable patients, the mean follow-up was 71.75 months (range, 2-154 months).

20

30

40

50

TIME (months)

interstitial tumors (6.2%), which has been previously noted,**'2*'8 the incidence of seminoma (42%)and nonseminoma (50%) is similar to other series of predominantly white patient^.'^^^'^^'^^^'^^^^^' Unlike our prior report, which found a 58.8% incidence of seminoma in blacks compared with 40% in the corresponding white population," the current series incidence is in line with expected incidence. Some prior reports suggested right-sided predominance in testicular tumors in blacks6,16whereas others

showed left-sided pred~minance.~,'~ Our study showed equal side distribution, which agrees with most series of black patients"," as well as reports of predominantly white patients." Five of 6 3 (7.9%)patients in our study had a history of undescended testicle, which agrees with most previously published reports on blacks6*'1~'2 as well as reports of predominantly white patients." The mean age overall and the mean age in nonseminoma are similar to that found in previous studies on black^^,'^ and predominantly white patient^.^,'^^'^ How-

% SURVIVORSHIP 100 80 60

40

Figure 3. Life table survival graph foi black patients with nonseminoma treated after the widespread use of cisplatin combination chemotherapy in 1980. For the 23 evaluable patients, the mean follow-up was 55.3 months (range, 1-128 months)

20 0 0

10

20

30

TIME (months)

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CANCER Ianuary 15, 2994, Volume 73,No. 2

ever, the mean age for blacks with seminoma in our study (29.6 years) is lower than that given in previous studies of predominantly white groups (range [mean], 35-37 year^).'^-^' Therefore, our study suggests that the black population has a mean age at diagnosis for seminoma 6-7 years younger than a predominantly white population. Delay in diagnosis in patients with testicular cancer is a significant problem. In a review of the literature describing 17 series of patients with testicular cancer since World War I1 encompassing over 4000 patients, Moul found an average delay of 24 weeks.33In another large single-institution review, the average delay was 39 weeks for seminoma, 14 weeks for nonseminoma, and 21 weeks overall.34Our study with a 20-week delay for seminoma, 11.5 weeks for nonseminoma, and 15.5 weeks overall is in line with these other general testis cancer data and indicates a similar problem of delay in diagnosis for black patients. However, the comparison of whites, with a mean delay of 16.7 weeks, and blacks, with a delay of 20.4 weeks, from a single institution, Walter Reed Army Medical Center, during the same time period in an equal-access health care environment is disturbing and suggests a greater propensity for delay in blacks. Considering that only 3 of 59 patients (5.1%) were initially seen after they had found a mass on testicular self -exam, better public awareness regarding this disease in this population is warranted.35 One would think that delay in diagnosis of testicular tumors would be prolonged by the erroneous diagnosis of epididymitis and treatment with antibiotics. However, our data show that this is not the case. Sixteen patients in our cohort were treated for epididymitis, and the mean delay in diagnosis for these patients was 14.4 weeks. This mean is actually lower than both the overall mean (15.5 weeks) and the mean for patients not diagnosed with epididymitis (16.0 weeks). When delay in diagnosis is compared for each tumor histology group, a correlation between longer delay in diagnosis and more benign pathology can be seen. The more malignant and more rapidly growing nonseminoma group was seen more quickly (1 1.5 weeks) than was the more indolent seminoma (20.3 weeks) and interstitial tumor (23.0 weeks) groups, which is similar to and well described in the general testis cancer population. Regarding prognosis, blacks and whites appear to have similar outlooks. As has been seen in general testis cancer cohorts; our data also support the effectiveness of cisplatin as a chemotherapeutic agent for nonsemin ~ r n aThe . ~ death ~ rate for nonseminoma dropped from 38% in 8 patients treated before the general use of cisplatin-based combination therapy in 1980 to 22% in 23 patients treated after 1980.

Twenty-one of 32 nonseminoma patients (65.3%) seen initially as late stage (IIB or 111) had an overall 72% survival rate (see Fig. 2). Thus, nonseminoma patients in our cohort tended to be seen initially at late stage and accounted for all seven cancer deaths in our study. All of these deaths occurred within 3 years of diagnosis. Conversely, seminoma patients were seen initially almost exclusively as Stage I or IIA and had no cancer deaths. This disparity between prognosis in seminoma and nonseminoma cancers in blacks is similar to that seen in studies of predominantly white populations.6.12,13.28.34,36 There was not an increase in the incidence of testis tumor in blacks compared with whites over the past 13 years. The incidence of testis cancer in blacks as a percentage of total cases treated at Walter Reed Army Medical Center from 1979 to 1991 shows no trend in either direction. The underlying reason why blacks do not have an incidence of testicular tumors similar to the white population is not well understood. Henderson et. al. postulated that increased testosterone levels in black women during early pregnancy compared with white women may provide a protective effect in testis cancer in male offspring3' The elevated testosterone is thought to provide a stimulus for progression of primitive germ cells to mature germ cells. Because primitive germ cells persisting into the pubertal period are thought to play a role in testis tumor development, the testosterone stimulus to mature germ cells provides a protective effect. This hypothesis needs further study and other factors may be involved. References 1. Koehler PR, FabrikantJI, Dickson RJ. Observations on the behavior of testicular tumors with comments on racial incidence. Urol 1962; 4~577-9. 2. Tiltman AJ.The racial incidence of testicular tumors. S Afr Med J 1969; 43~97-8. 3. Tulinius H, Day N, Muir CS. Rarity of testis cancer in negroes. Lancet 1973; 2:35-6. 4. Sherman FP, Ciavarra VA, Cohen MJ. Testis tumors in negroes. Urology 1973; 2:318-20. 5. Berg JW, Godwin JD, McKay FW, Percy CL. Testis cancer in negroes. Lancet 1973; 1:782-3. 6. Keller AZ. Testicular cancer in blacks and whites by cell types, laterality, survivorship, and age. J Natl Med Assoc 1974; 66:4952. 7. Mustacchi P, Millrnore D. Racial and occupational variations in cancer of the testis: San Fransisco, 1956-65. J Natl Cancer lnst 1976; 56~717-20. 8. Onuigbo WIB. Relevance of race in management of testicular tumours. Br Med 1977; 1:22-3. 9. Coovadia YM. Primary testicular tumours among white, black and Indian patients. S Am Med J 1978; 54:351-2. 10. Zimrnerman RR, Kung'U A. Testicular neoplasms in Kenyan Africans. Cancer 1978; 41:2452-5.

Testicular Cancer in Blacks/Moul et al. 11. Rao AB, Sparke B. Tumours of testis in Jamaica. Br J Urol 1979; 511151-3. 12. Daniels JL, Stutzman RE, McLeod DG. A comparison of testicular tumors in black and white patients. J Urol 1981; 125:341-2. 13. McDonald MW, Johnson DE, Guinee VF. Testicular tumors in blacks. Urology 1984; 23:543-6. 14. Sagalowsky Al, Admire RC. Increasing incidence of testicular cancer in blacks. Urology 1985; 26:558-60. 15. Brown LM, Pottern LM, Hoover RN, Devesa SS, Aselton P, Flannery JT. Testicular cancer in the United States: trends in incidence and mortality. Int J Epidemiol 1986; 15:164-70. 16. Spitz MR, Sider JG, Pollack ES, Lynch HK, Newell GR. Incidence and descriptive features of testicular cancer among United States whites, blacks, and Hispanics, 1973-1982. Cancer 1986; 58:1785-90. 17. Newell GR, Spitz MR, Sider JG, Pollack ES. Incidence of testicular cancer in the United States related to marital status, histology, and ethnicity. ] N a t l Cancer Inst 1987; 78:881-5. 18. Van den Eeden SK, Weiss NS. Is testicular cancer incidence in blacks increasing? American Journal of Public Health 1989; 79:1553-4. 19. Onuora VC, Akumabor PN, Aghahowa ]A. Non-germ cell testicular tumours in Nigerians. Trop Geogr Med 1989; 41:358-60. 20. Schrek R. The racial distribution of cancer. Ann Surg 1944; 120:809-12. 21. Morrison AS. Some social and medical characteristics of Army men with testicular cancer. Am J Epidemiol 1976; 104:511-6. 22. Young JL, Devesa SS, Cutler SJ. Incidence of cancer in United States blacks. Cancer Res 1975; 35:3523-36. 23. Dean AG, Dean JA, Burton AH, Dicker RC. Epi. Info, Version 5: a word processing, database, and statistics program for epidemiology on microcomputers. Stone Mountain, GA: USD Inc., 1990. 24. Norvisis/SPSS Inc. SPSS/PC+ Advanced Statistics 4.0. Chicago: SPSS Inc., 1990.

393 25. Dixon FJ, Moore RA. Tumors of the male sex organs. In: Atlas of tumor pathology. 31st ed., vol. 32. Washington, DC: Armed Forces Institute of Pathology, 1952. 26. Friedman NB, Moore,RA. Tumors of the testis. Military Surgeon 1946; 99:573-93. 27. Garland FC, Gorham ED, Garland CF, Ducatman AM. Testicular cancer in US Navy personnel. Am J Epidemiol 1988; 127:4114. 28. Raines SL, Hurdle TG. Tumors of the testis. J Urol 1955; 73:36372. 29. Reedy EK, Burke M, Shanller G, Krishman L, Gener L, Evans R, et al. Testicular neoplasms: seminoma. J Nutl Med Assoc 1990; 82:651-5. 30. Ellerbrook NA, Tran LM, Selch MT, Taylor JMG, Parker RG. Testicular seminoma. A m J Clin Oncol 1988; 11:93-9. 31. Hannun Y, Vugrin D. Long-term survival in patients treated for testicular seminoma. ] Surg Oncol 1990; 43:177-80. 32. Epstein BE, Order,SE, Zinreich E. Staging, treatment, and results in testicular seminoma. Cancer 1990; 65:405-11. 33. Moul JW. Pitfalls in the management of testis cancer and complications of therapy. In: Rous SN, editor. Urology annual. New York: Norton, 1992:161-97. 34. Moul JW, Paulson DF, Dodge RK, Walther PJ, Delay in diagnosis and survival in testicular cancer: Impact of effective therapy and changes during 18 years. J Urol 1990; 143:520-3. 35. Millon-Underwood S, Sanders E. Testicular self-exam among African-American men. J N a t l Black Nurses Assoc 1991; 5:18-28. 36. Moul JW, Dodge RK, Robertson JE, Paulson DF, Walther PJ. The impact of the “cisplatin era” of treatment on survival in testicular cancer. World J Urol 1991; 9:45-50. 37. Henderson BE, Bernstein L, Ross RK, Depue RH, Judd HL. The early in-utero oestrogen and testosterone environment of blacks and whites: potential effects on male offspring. BrJ Cancer 1988; 57~216-8.