ABSTRACT
Background
Testicular germ cell tumors (TGCTs) are the most common cancers among young men in the United States. Incidence rates among non‐Hispanic White (NHW) men historically have been much higher than the rates among other men. To study whether this pattern had changed, the authors examined trends in TGCT incidence for the years 1992–2021.
Methods
By using the Surveillance, Epidemiology, and End Results 12 registries database, age‐standardized incidence rates per 100,000 person‐years and 95% confidence intervals (CIs) were calculated overall and by histologic type (seminoma and nonseminoma), age, stage at diagnosis, and race/ethnicity. Trends in 5‐year survival also were examined.
Results
The age‐standardized incidence rate of TGCT per 100,000 person‐years increased from 4.71 (95% CI, 4.39–5.05) in 1992 to 6.22 (95% CI, 5.88–6.58) in 2021. The rates increased for both seminoma (average annual percent change [AAPC], 0.57%; 95% CI, 0.40%–0.75%) and nonseminoma (AAPC, 1.41%; 95% CI, 1.17%–1.64%) and among all race/ethnic groups, although the rates stabilized among NHW men. Increases in incidence were greatest among Hispanic men (AAPC, 3.03%; 95% CI, 2.66%–3.40%), who had one of the youngest median ages at diagnosis and were more likely to be diagnosed at advanced stages compared with NHW men. Seminoma and nonseminoma rates among Hispanic men converged over the study period, whereas seminoma rates remained higher among most other groups.
Conclusions
Hispanic men now have the highest TGCT incidence rates in the United States, although the rates increased among all groups between 1992 and 2021. Racial/ethnic differences in rates require further investigation.
Keywords: incidence, survival, testicular cancer, testicular germ cell tumors, trends, United States
Short abstract
Testicular cancer age‐standardized incidence rates per 100,000 person‐years increased from 4.71 (95% confidence interval, 4.39–5.05) in 1992 to 6.22 (95% confidence interval, 5.88–6.58) in 2021, primarily driven by increases in nonseminoma, and the greatest increases were observed among Hispanic men. Further investigations into the risk factors associated with changes over recent decades, such as endocrine‐disrupting chemicals, other maternal exposures, and/or gene–environment interactions, are warranted.
INTRODUCTION
Testicular cancer is the second most commonly diagnosed cancer among men aged 15–39 years globally and the most commonly diagnosed cancer among this group in the United States, with an age‐standardized global incidence rate of 1.7 per 100,000 person‐years in 2022. 1 The majority of testicular cancers are testicular germ cell tumors (TGCTs; 98%), 2 which can be further classified as seminomas, nonseminomas, and spermatocytic tumors. 3 , 4 Although the prognosis of TGCT is generally favorable in areas with the highest incidence (e.g., Western and Northern Europe, North America, Australia), 3 , 5 incidence rates have been increasing over time in many countries worldwide. 6
A prior analysis by our group indicated that the greatest increases in TGCT incidence rates in the United States between 2001 and 2016 were among Asian/Pacific Islander (API) men (average annual percent change [AAPC], 2.47%), Hispanic men (AAPC, 2.10%), and American Indian/Alaska Native (AIAN) men (AAPC, 1.71%), although rates also increased among other racial/ethnic groups (AAPC: non‐Hispanic Black [NHB] men, 1.28%; non‐Hispanic White [NHW] men, 0.41%). 7
Established risk factors for TGCT include cryptorchidism, 8 , 9 inguinal hernia, 8 , 9 hypospadias, 8 and being a twin, 9 as well as genetic 10 , 11 and environmental factors. 2 , 12 , 13 However, TGCT etiology remains poorly understood, and increases in incidence are not fully explained by known risk factors. The objective of the current analysis was to examine recent incidence trends by histologic type, age, birth cohort, stage at diagnosis, and race/ethnic group. Relative 5‐year survival rates were also assessed.
MATERIALS AND METHODS
Data sources
TGCT incidence data were obtained from the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. The SEER 12 registries (SEER‐12) database represents roughly 12% of the total US population and includes the following state and regional cancer registries: Alaska Native Tumor Registry, Atlanta, Connecticut, Hawaii, Iowa, Los Angeles, New Mexico, Rural Georgia, San Francisco‐Oakland, San Jose‐Monterey, Seattle‐Puget Sound, and Utah. 14 SEER data are considered to be high quality and capture all US racial/ethnic groups, allowing for analyses among diverse US populations. 15 TGCTs and histologic types were classified using the International Classification of Diseases for Oncology, 3rd edition (i.e., using the SEER site recode variable) topography code C62 and morphology codes 9060–9062, 9064 (seminomas), and 9065–9102 (nonseminomas). 16 Spermatocytic tumors (morphology code 9063), which account for only 0.6% of all TGCTs, 17 were not examined in the current analysis because these tumors are believed to have an etiology distinct from that of seminomas and nonseminomas.
Statistical analyses
Age‐standardized incidence rates (ASR) per 100,000 person‐years and 95% confidence intervals (CIs) were calculated by race/ethnicity (Hispanic, NHW, NHB, API, and AIAN) and by histologic type (all TGCTs, seminoma, or nonseminoma) for the years 1992–2021. Ethnicity (i.e., origin) in the SEER database is categorized according to the North American Association of Central Cancer Registries (NAACCR) Hispanic Identification Algorithm (NHIA). 18 AIAN status was determined by SEER Purchased/Referred Care Delivery Area (2000 variable) identification. Rates by stage at diagnosis (localized, regional, or distant), classified according to the SEER Summary Stage 2000 variable, 19 were calculated by race/ethnicity. In addition, age at diagnosis and relative 5‐year survival rates were extracted from the SEER database.
Estimated annual percent change (EAPC) trends and 95% CIs were calculated using a joinpoint regression model of the natural log‐transformed rates. A joinpoint model allows for nonlinear trends in incidence over time and assigns a joinpoint at which the trend significantly changes using a Monte Carlo permutation method. 20 Where one or more joinpoints were incorporated into the model, the AAPC was calculated to characterize the entire study period (1992–2021). If no joinpoints were identified, the AAPC was the same as the EAPC. In the current analysis using the default maximum number of joinpoints, a maximum of five joinpoints were allowed in the model. In addition, trends in seminoma and nonseminoma incidence rates over time were compared using pairwise tests of parallelism based on segmented line regression models. 21 A lack of parallelism is indicated when the permutation test indicates that assigned joinpoints, and the resulting AAPC in rates, differ significantly between seminomas and nonseminomas. To conduct a sensitivity analysis, the SEER‐12 rates were compared with rates from the SEER‐22 database because SEER‐22 includes a larger proportion of the US population, but coverage only started in year 2000.
By using the direct method, rates were adjusted to the 2000 US standard population and were calculated using the SEER*Stat version 8.4.0 software program (IMS, Inc.). Joinpoints, EAPCs, AAPCs, and tests for parallelism were calculated using the Joinpoint Regression Program version 4.9.0.0 (IMS, Inc.). Other data analysis was performed in SAS version 9.4 (SAS Institute Inc.). All tests for significance were two‐sided, and p values < .05 without adjustment for multiple comparisons were considered statistically significant.
RESULTS
TGCT incidence rates increased among all men over the 29‐year study period. The overall incidence rate increased from 4.71 cases per 100,000 person‐years (95% CI, 4.39–5.05) in 1992 to 6.22 (95% CI, 5.88–6.58) in 2021 (Table 1). The AAPC was significantly greater than zero overall (AAPC, 0.92%; 95% CI, 0.79%–1.06%) and among all racial/ethnic groups except NHB men (AAPC, −0.95%; 95% CI, −2.08%, 1.93%). Increases in incidence over the study period were greatest among Hispanic men (AAPC, 3.03%; 95% CI, 2.66%–3.40%) followed by AIAN men (AAPC, 2.8%; 95% CI, 1.22%–4.41%). Incidence among Hispanic men more than doubled from 1992 to 2021 (1992 [ASR per 100,000 person‐years, 3.22; 95% CI, 2.60–4.01] vs. 2021 [ASR per 100,000 person‐years, 7.58; 95% CI, 6.88–8.34]), surpassing rates among NHW men by 2021.
TABLE 1.
Testicular germ cell tumor age‐standardized incidence rates overall and by race/ethnicity: Surveillance, Epidemiology, and End Results 12 registries, United States, 1992–2021.
| 1992 | 2021 | Joinpoint | EAPC trend, % a | AAPC b | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of cases c | ASR | 95% CI | No. of cases c | ASR | 95% CI | Year | 1 | 2 | % | 95% CI | |
| TGCT | 835 | 4.71 | 4.39–5.05 | 1266 | 6.22 | 5.88–6.58 | — | 0.92 d | — | 0.92 d | 0.79–1.06 |
| Race/ethnicity | |||||||||||
| Non‐Hispanic White | 666 | 6.14 | 5.68–6.63 | 659 | 7.15 | 6.60–7.72 | 2004 | 1.74 d | −0.01 | 0.71 d | 0.36–1.07 |
| Non‐Hispanic Black | 11 | 0.68 | 0.33–1.34 | 19 | 1.00 | 0.59–1.59 | 2016 | 1.53 d | −7.54 | —0.95 | —2.08–1.93 |
| American Indian/Alaska Native | 7 | 3.15 | 1.24–7.66 | 12 | 4.72 | 2.40–8.43 | — | 2.80 d | — | 2.80 d | 1.22–4.41 |
| Asian/Pacific Islander | 33 | 1.89 | 1.29–2.70 | 89 | 2.71 | 2.17–3.34 | — | 1.44 d | — | 1.44 d | 0.90–1.98 |
| Hispanic | 116 | 3.22 | 2.60–4.01 | 437 | 7.58 | 6.88–8.34 | — | 3.03 d | — | 3.03 d | 2.66–3.40 |
| Seminoma | 478 | 2.78 | 2.53–3.05 | 692 | 3.42 | 3.17–3.69 | — | 0.57 d | — | 0.57 d | 0.40–0.75 |
| Race/ethnicity | |||||||||||
| Non‐Hispanic White | 397 | 3.65 | 3.30–4.03 | 392 | 4.19 | 3.78–4.63 | 2004 | 1.62 d | −0.19 | 0.56 d | 0.13–0.99 |
| Non‐Hispanic Black | 5 | 0.33 | 0.10–0.92 | 12 | 0.65 | 0.33–1.15 | 1997 | 14.83 | −1.19 | 1.40 | −1.49–4.34 |
| American Indian/Alaska Native | 2 | 0.86 | 0.10–4.74 | 4 | 1.67 | 0.44–4.43 | — | 2.98 d | — | 2.98 d | 0.59–5.42 |
| Asian/Pacific Islander | 16 | 1.01 | 0.57–1.69 | 52 | 1.61 | 1.20–2.12 | — | 0.69 | — | 0.69 | —1.16–1.56 |
| Hispanic | 57 | 1.75 | 1.27–2.40 | 199 | 3.61 | 3.12–4.16 | — | 2.52 d | — | 2.52 d | 2.03–3.00 |
| Nonseminoma | 357 | 1.93 | 1.73–2.15 | 574 | 2.81 | 2.58–3.05 | — | 1.41 d | — | 1.41 d | 1.17–1.64 |
| Race/ethnicity | |||||||||||
| Non‐Hispanic White | 269 | 2.49 | 2.20–2.81 | 267 | 2.96 | 2.61–3.34 | — | 0.85 d | — | 0.85 d | 0.53–1.17 |
| Non‐Hispanic Black | 6 | 0.35 | 0.13–0.91 | 7 | 0.35 | 0.13–0.76 | — | 1.79 d | — | 1.79 d | 0.30–3.31 |
| American Indian/Alaska Native | 5 | 2.28 | 0.72–6.60 | 8 | 3.04 | 1.29–6.21 | — | 2.28 d | — | 2.28 d | 0.38–4.22 |
| Asian/Pacific Islander | 17 | 0.88 | 0.51–1.46 | 37 | 1.20 | 0.77–1.53 | — | 2.48 d | — | 2.48 d | 1.55–3.42 |
| Hispanic | 59 | 1.47 | 1.09–2.01 | 238 | 3.97 | 3.48–4.52 | — | 3.60 d | — | 3.60 d | 3.08–4.12 |
Abbreviations: AAPC, average annual percent change; ASR, age‐standardized incidence rate per 100,000 person‐years; CI, confidence interval; EAPC, estimated annual percent change; TGCT, testicular germ cell tumor.
aThe EAPC reflects whether a change in the rate for a particular time segment was statistically significant.
bThe AAPC reflects whether a change in the rate for the entire time interval (1992–2021) was statistically significant.
cCases may not add up to the total number because of unknown race/ethnicity information (data not shown).
dThe trend was statistically different from zero at alpha = .05.
The nonseminoma AAPC in rates were significantly greater than zero (AAPC, 1.41%, 95% CI, 1.17%–1.64%) overall and among all groups. The largest AAPC was seen among Hispanic men and the smallest among NHW men. The seminoma AAPCs were more varied. The overall seminoma AAPC was significantly greater than zero (AAPC, 0.57%; 95% CI, 0.40%–0.75%) but smaller than that observed for nonseminoma. Although the rates in seminoma AAPCs were significant among NHW, AIAN, and Hispanic men, they were nonsignificant among NHB and API men. In 2021, seminoma rates were higher than nonseminoma rates among NHW, NHB, and API men. Among AIAN and Hispanic men, nonseminoma incidence rates were higher than seminoma rates, although the rates were similar among Hispanic men.
The only decreases in rates were observed for TGCTs overall among NHW men from 2004 to 2021 (EAPC trend, −0.01%), driven by seminomas (EAPC trend, −0.19%), and among NHB men from 2016 to 2021 (EAPC trend, −7.54%), also driven by seminomas (EAPC trend, −1.19%). Both decreases were nonsignificant.
Between 1992 and 2021, seminoma rates remained higher than nonseminoma rates overall and among NHW, NHB, and API men. Only among Hispanic men did seminoma and nonseminoma incidence rates converge, and only among AIAN men were nonseminoma rates consistently higher than seminoma rates.
In the SEER‐22 analysis, the results were similar (see Table S1), although incidence rates among Hispanic men surpassed rates among NHW men only for nonseminoma.
Changes in rates over the study period are displayed on a log scale in 3‐year groupings in Figure 1. Reflecting the AAPCs presented in Table 1, seminoma and nonseminoma incidence increased gradually over the study period. Among NHW men, rates for both histologic types plateaued around the 2004–2006 interval, although seminoma rates stabilized slightly earlier than nonseminoma rates. Whereas seminoma and nonseminoma trends among NHW and AIAN men appeared similar throughout the study period, significant differences in trends between histologic types were observed among NHB men (pairwise test of parallelism, p = .032), API men (p = .009), and Hispanic men (p = .005).
FIGURE 1.
Age‐standardized TGCT incidence rate trends by race/ethnicity and histologic subtype, Surveillance, Epidemiology, and End Results 12 registries, United States, 1992–2021 (p values reflect whether there were significant differences between the trends in seminoma and nonseminoma rates). AIAN indicates American Indian/Alaska Native; API, Asian/Pacific Islander; ASR, age‐standardized incidence rate per 100,000 person‐years; NHB, non‐Hispanic Black; NHW, non‐Hispanic White; TGCT, testicular germ cell tumor.
The median age at diagnosis and the interquartile range (IQR; quartiles 1–3) by race/ethnicity and histologic type are presented in Table 2. The median age at diagnosis of TGCTs among all men combined was 33 years (2019–2021: IQR, 27–40 years). Notably, age at diagnosis was observed to be youngest among AIAN and Hispanic men. Among AIAN men, the median age at TGCT diagnosis was youngest (median, 26 years; IQR, 23–31 years) in the 2004–2006 interval, then rose to 30 years (IQR, 24.5–40.5 years) in the later time intervals. Among Hispanic men, the median age at diagnosis remained in the range of 28–29 years during the entire study period. Conversely, the median age at TGCT diagnosis was highest among NHB men in almost all intervals.
TABLE 2.
Testicular germ cell tumor median age at diagnosis and interquartile range by race/ethnicity and histologic type: Surveillance, Epidemiology, and End Results 12 registries, United States, 1992–2021.
| Year of diagnosis | Age at diagnosis, years | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall | NHW | NHB | AIAN | API | Hispanic | |||||||
| Median | IQR | Median | IQR | Median | IQR | Median | IQR | Median | IQR | Median | IQR | |
| TGCT | ||||||||||||
| 1992–1994 | 33 | 27–39 | 34 | 28–40 | 34 | 27–37 | 27 | 22–34 | 33.5 | 27–40 | 29 | 24–35 |
| 1995–1997 | 33 | 27–40 | 34 | 28–41 | 36 | 31–42 | 29 | 25–39 | 33 | 27–38 | 29 | 24–35 |
| 1998–2000 | 34 | 27–41 | 35 | 28–42 | 37 | 28–44 | 31 | 28–38 | 34 | 26–42 | 28 | 23–35 |
| 2001–2003 | 34 | 27–41 | 35 | 28–42 | 33.5 | 26–40 | 30 | 24–35 | 32 | 25.5–39 | 29 | 23–35 |
| 2004–2006 | 33 | 26–41 | 34 | 27–42 | 35.5 | 29–44 | 26 | 23–31 | 33 | 26–42 | 29 | 24–35 |
| 2007–2009 | 32 | 25–41 | 34 | 27–43 | 36 | 28–43 | 34.5 | 27.5–43 | 30 | 24–39 | 28 | 23–35 |
| 2010–2012 | 33 | 26–42 | 34 | 27–44 | 36 | 28–45 | 31.5 | 27–41 | 32 | 26–41 | 28 | 23–36 |
| 2013–2015 | 32 | 26–41 | 34 | 27–44 | 38 | 31–45 | 30 | 25–40 | 31 | 26–38 | 28 | 23–35 |
| 2016–2018 | 32 | 26–40 | 34 | 28–43 | 37 | 29–42 | 30 | 26–39.5 | 32 | 26–40 | 28 | 23–36 |
| 2019–2021 | 33 | 27–40 | 35 | 29–43 | 37 | 29–45 | 30 | 24.5–40.5 | 32 | 27–41 | 29 | 24–35 |
| Seminoma | ||||||||||||
| 1992–1994 | 36 | 30–42 | 36 | 31–42 | 35 | 29–38 | 30 | 26–35 | 36 | 31–41 | 32 | 28–38 |
| 1995–1997 | 36 | 31–42 | 37 | 32–43 | 35 | 31–42 | 37 | 31–44 | 35 | 31–43 | 32 | 28–38 |
| 1998–2000 | 37 | 31–43 | 37 | 32–43 | 39 | 33–45 | 28 | 28–38 | 38 | 31–43 | 33 | 27–39 |
| 2001–2003 | 37 | 31–43 | 38 | 32–44 | 37 | 30–43 | 35 | 30–36 | 35 | 28–40 | 32 | 28–38 |
| 2004–2006 | 37 | 30–44 | 37 | 31–45 | 39 | 33–46 | 29 | 25–34 | 38 | 29–46 | 33 | 28–40 |
| 2007–2009 | 36 | 29–45 | 38 | 30–46 | 38 | 31–43 | 35 | 28–44 | 36 | 29.5–43.5 | 32 | 26–38 |
| 2010–2012 | 37 | 30–45 | 38 | 32–47 | 38 | 33–46 | 36 | 29–44 | 36 | 30–45 | 32 | 27–41 |
| 2013–2015 | 36 | 30–46 | 38 | 31–48 | 41 | 35–46 | 36 | 28–45 | 35 | 29–42 | 33 | 27–39 |
| 2016–2018 | 36 | 30–45 | 38 | 32–48 | 38 | 34–43 | 33 | 30–46 | 36 | 31–42 | 33 | 28–39 |
| 2019–2021 | 36 | 30–44 | 37 | 31–47 | 38 | 30–47 | 37 | 30–45 | 36 | 30–44 | 33 | 28–38 |
| Nonseminoma | ||||||||||||
| 1992–1994 | 28 | 23–34 | 29 | 24–35 | 31 | 24–35 | 25 | 21–32 | 26 | 22–33 | 25 | 20–31 |
| 1995–1997 | 29 | 23–35 | 30 | 24–36 | 38 | 26–45 | 25 | 22–27 | 25 | 18.5–33.5 | 26 | 21–31 |
| 1998–2000 | 29 | 23–35 | 30 | 24–36 | 30 | 22–38 | 32 | 25.5–39 | 26 | 21–33 | 25 | 21–31 |
| 2001–2003 | 29 | 22–36 | 30 | 24–37 | 27 | 20–37 | 24 | 20–30 | 26 | 21–31 | 25 | 20–30 |
| 2004–2006 | 28 | 22–35 | 29 | 24–37 | 29 | 25–39 | 25 | 22–27.5 | 27 | 21–35 | 25 | 21–30 |
| 2007–2009 | 27 | 22–34 | 29 | 23–35 | 32 | 22–44 | 30 | 25–37 | 25 | 20–30 | 24.5 | 20–29 |
| 2010–2012 | 27 | 22–34 | 28 | 23–36 | 32 | 23–39 | 27 | 23–29 | 26.5 | 22–34 | 25 | 21–30 |
| 2013–2015 | 28 | 23–34 | 29 | 24–36 | 32 | 29–40 | 27 | 24–31 | 27 | 23–32 | 25 | 21–30 |
| 2016–2018 | 28 | 23–34 | 29 | 24–36 | 32 | 25–40 | 26 | 23–30 | 28 | 24–33 | 25 | 21–30 |
| 2019–2021 | 29 | 24–35 | 31 | 25–37 | 35 | 27–42 | 24 | 21–29 | 29 | 23–35 | 26 | 22–32 |
Abbreviations: AIAN, American Indian/Alaska Native; API; Asian/Pacific Islander; IQR, interquartile range; NHB, non‐Hispanic Black; NHW, non‐Hispanic White; TGCT, testicular germ cell tumor.
In the 2019–2021 interval, the median age at diagnosis of seminoma (36 years; IQR, 30–44) was older than that of nonseminoma (29 years; IQR, 24–35 years). In this time period, the median age at diagnosis of seminoma (36–38 years) was similar among all groups except Hispanic men, who had a median age at diagnosis of 33 years (IQR, 28–38 years). Greater variability was observed in the median age at diagnosis of nonseminoma, with NHW and NHB men diagnosed at older ages (31–35 years) than AIAN men (24 years), API men (29 years), and Hispanic men (26 years).
TGCTs diagnosed in 2021 by stage at diagnosis and by race/ethnicity are displayed in Figure 2. Among all race/ethnic groups, the majority of TGCTs were diagnosed as localized (65.7%), whereas 22.4% were regional, and 12.9% were distant (see Table S2). NHW men (66.6%) and API men (66.3%) had the highest proportions of localized tumors. Conversely, TGCTs were more likely diagnosed as distant among AIAN men (33.3%), NHB men (21.1%), and Hispanic men (17.3%). Furthermore, AIAN men had the highest proportion of nonlocalized tumors of all race/ethnic groups examined (66%).
FIGURE 2.
Testicular germ cell tumor cases diagnosed in 2021 by stage at diagnosis and race/ethnicity: Surveillance, Epidemiology, and End Results 12 registries, United States. AIAN indicates American Indian/Alaska Native; API, Asian/Pacific Islander; NHB, non‐Hispanic Black; NHW, non‐Hispanic White.
Relative 5‐year survival rates for TGCTs were high; roughly 96% of those diagnosed survived at least 5 years overall (Table 3). Survival was observed to be better for seminoma than nonseminoma; 5‐year survival for 2016–2017 was 98.3% for seminoma versus 92.5% for nonseminoma, which was consistent throughout the study period and when examined both overall and by race/ethnicity. Survival rates were observed to be relatively stable over the entire study period, particularly among NHW men. Hispanic, NHB, and AIAN men generally had poorer survival for both seminoma and nonseminoma compared with NHW and API men. Furthermore, survival among Hispanic and NHB men appeared to be trending downward in recent years, particularly for nonseminoma.
TABLE 3.
Relative 5‐year survival rates for testicular germ cell tumors overall and by race/ethnicity: Surveillance, Epidemiology, and End Results 12 registries, 1992–2017.
| Year of diagnosis | 5‐year survival, % | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TGCT | Seminoma | Nonseminoma | ||||||||||||||||
| Overall | NHW | NHB | AIAN | API | Hispanic | Overall | NHW | NHB | AIAN | API | Hispanic | Overall | NHW | NHB | AIAN | API | Hispanic | |
| 1992–1993 | 94.5 | 95.7 | 82.8 | 100.0 | 93.2 | 89.5 | 96.9 | 97.7 | 88.5 | 100.0 | 96.2 | 93.1 | 90.9 | 92.4 | 73.8 | 100.0 | 87.1 | 85.1 |
| 1994–1995 | 96.6 | 97.2 | 98.1 | 100.0 | 94.9 | 93.2 | 97.7 | 98.3 | 96.0 | 100.0 | 95.9 | 94.6 | 94.9 | 95.3 | 100.0 | 100.0 | 93.0 | 91.2 |
| 1996–1997 | 95.6 | 96.1 | 87.0 | 84.2 | 92.4 | 95.4 | 97.2 | 98.1 | 93.8 | 79.1 | 91.4 | 95.1 | 93.3 | 93.0 | 50.7 | 89.9 | 94.7 | 95.5 |
| 1998–1999 | 95.4 | 96.2 | 91.4 | 84.9 | 93.7 | 92.3 | 97.7 | 97.9 | 97.0 | 100.0 | 96.0 | 96.4 | 91.6 | 93.3 | 78.0 | 71.7 | 88.7 | 87.7 |
| 2000–2001 | 96.3 | 97.4 | 94.1 | 90.6 | 95.7 | 91.5 | 98.3 | 99.3 | 96.8 | 88.5 | 96.6 | 93.2 | 93.2 | 94.1 | 89.2 | 92.0 | 93.4 | 89.8 |
| 2002–2003 | 96.7 | 97.7 | 83.6 | 90.6 | 91.1 | 94.7 | 98.1 | 98.3 | 96.3 | 90.7 | 89.6 | 99.4 | 94.4 | 96.6 | 50.3 | 94.1 | 93.1 | 88.6 |
| 2004–2005 | 95.9 | 97.2 | 89.9 | 90.6 | 94.3 | 91.6 | 98.6 | 98.4 | 97.0 | 100.0 | 98.0 | 98.5 | 92.4 | 95.5 | 77.2 | 82.9 | 89.3 | 85.9 |
| 2006–2007 | 95.5 | 96.6 | 94.0 | 90.6 | 92.4 | 92.7 | 97.6 | 98.3 | 91.6 | 90.8 | 98.0 | 95.5 | 92.8 | 94.2 | 96.1 | 86.4 | 84.3 | 90.2 |
| 2008–2009 | 97.0 | 98.1 | 91.2 | 90.6 | 95.8 | 94.5 | 98.8 | 99.1 | 97.1 | 92.0 | 98.0 | 97.5 | 94.6 | 96.4 | 77.2 | 79.6 | 94.5 | 91.4 |
| 2010–2011 | 96.9 | 97.8 | 92.3 | 90.6 | 93.9 | 94.8 | 98.9 | 98.8 | 100.0 | 100.0 | 98.0 | 98.0 | 93.8 | 95.7 | 81.3 | 92.1 | 89.6 | 91.2 |
| 2012–2013 | 96.2 | 97.2 | 93.8 | 90.6 | 96.4 | 93.5 | 97.4 | 98.4 | 100.0 | 87.5 | 98.0 | 93.0 | 94.6 | 95.7 | 85.2 | 78.7 | 89.6 | 93.9 |
| 2014–2015 | 96.3 | 97.2 | 91.9 | 90.6 | 95.0 | 94.5 | 97.8 | 98.1 | 93.7 | 85.7 | 98.0 | 96.9 | 94.4 | 95.8 | 88.4 | 91.2 | 91.9 | 92.3 |
| 2016–2017 | 95.6 | 97.2 | 85.8 | 90.6 | 93.6 | 92.8 | 98.3 | 98.5 | 92.7 | 94.9 | 98.0 | 97.4 | 92.5 | 94.6 | 80.1 | 100.0 | 90.3 | 89.1 |
Abbreviations: AIAN, American Indian/Alaska Native; API, Asian/Pacific Islander; NHB, non‐Hispanic Black; NHW, non‐Hispanic White; TGCT, testicular germ cell tumor.
Figure 3 displays the age‐specific incidence rates for men born in the years 1950–2009 by birth cohort. The rates were generally observed to be lowest among those born in the earliest cohorts and highest among the 1990–1999 birth cohort overall and for nonseminoma. Greater variation was observed in rates between birth cohorts for nonseminomas than for seminomas, particularly among those diagnosed at younger ages.
FIGURE 3.
Age‐standardized incidence rates of TGCT by birth cohort overall and by histologic type, Surveillance, Epidemiology, and End Results 12 registries, United States, 1992–2021. ASR indicates age‐standardized incidence rate per 100,000 person‐years; TGCT, testicular germ cell tumor.
DISCUSSION
TGCT incidence rates in the United States have been rising for some time, although rates among NHW men previously had been consistently higher. 17 Between 1992 and 2021, seminoma remained the predominant histologic TGCT type, but nonseminoma rates generally increased at a faster rate. Although NHW men had the largest burden of cases, incidence rates, particularly for seminoma, stabilized while rates among other racial/ethnic groups continued to rise for both seminoma and nonseminoma. This was most evident among Hispanic men, in whom the rates of both seminoma and nonseminoma more than doubled over the study period.
Our study supports previous findings that TGCT rates are rising in the United States 17 and that the incidence gap between lower and higher risk populations has been narrowing. 6 We observed that, in recent years, rates among Hispanic men caught up to the rates among NHW men. Our study also indicated that Hispanic men: (1) had similar rates of seminoma and nonseminoma, whereas NHW men, as well as NHB men and API, had higher rates of seminoma; (2) had a greater proportion of TGCTs diagnosed at distant stage compared with NHW men; and (3) were diagnosed with both seminoma and nonseminoma at younger ages than NHW men. Some of these differences may be explained by demographic factors; for example, the younger median age at diagnosis among Hispanic men may be attributed to differences in the underlying age structure of the populations. 22 In addition, previous studies have demonstrated that barriers to health care, such as health insurance coverage, could explain later stages at diagnosis among Hispanic men. 14
A recent study using NAACCR cancer registry data reported increasing incidence rate ratios with successive birth cohorts among several cancers, including testicular cancer. 23 Those findings are similar to our current findings, in which rates were highest among the 1990–1999 birth cohort overall and for nonseminoma. The 1990–1999 birth cohort also had the highest rate of seminoma diagnosed at ages 30–34 years. As that cohort ages, rates are likely to remain higher than among prior birth cohorts. Similarly, rates among men born in 2000 or later may eventually surpass rates observed among the 1900–1999 birth cohort. The differences by birth cohort suggest that environmental or behavioral factors are likely to be important contributors to the observed increases in incidence.
Risk factors for TGCTs are not fully elucidated, although TGCT has been suggested to be part of a testicular dysgenesis syndrome that also includes hypospadias, cryptorchidism, and inguinal hernia. 2 , 9 All the conditions are hypothesized to be a consequence of genetic and endocrine‐disrupting factors. 24 In addition, family history of TGCT and European ancestry have been linked to TGCT. 10 , 25 However, in previous studies in which the genetic susceptibility of NHW and Hispanic men with TGCT were examined, no difference by race/ethnicity was identified. 26 , 27 Considering this evidence, and because genetic factors alone are unlikely to explain the increasing incidence rates, other nongenetic factors almost certainly contribute to TGCT risk.
Epidemiologic evidence has reported that maternal exposure to endocrine‐disrupting chemicals, such as perfluorooctanoic acid, dichlorodiphenyl dichloroethylene, and chlordane compounds, are associated with increased testicular cancer risk among offspring. 13 , 28
In addition, maternal exposure to phthalates 29 has been reported to increase risk. 30 , 31 Observed associations between endocrine‐disrupting chemicals and nonseminomas tend to be stronger than associations with seminomas. 30 This could partially explain the difference in histology patterns observed between Hispanic men and other race/ethnic groups because prior analyses have indicated that urinary concentrations of these chemicals are higher among Hispanic men than among NHW men. 32 , 33 , 34
A major strength of the current study is the use of high‐quality, population‐based cancer registry data to estimate incidence and survival. In addition, histology information was available for nearly all TGCT cases in SEER‐12 (>99%), allowing for analyses by histologic type.
A limitation of the current analysis is that some racial/ethnic groups (in particular NHB and AIAN men) had very small case counts. Therefore, conclusions about the trends in these groups are not as reliable as conclusions about other groups. In addition, the analysis of the most recent rates in SEER‐22 indicated that the rates among Hispanic men, although increasing, had not yet surpassed the rates among NHW men. This difference between SEER‐12 and SEER‐22 is likely related to several factors, including the greater representation of Hispanic persons in SEER‐22 as well as a greater diversity of ancestry and birth country in SEER‐22. Our analysis also lacked granularity in racial/ethnic categorization of some groups. Because of the aggregated nature of SEER data, API, AIAN, and Hispanic race/ethnic groups could not be examined by ancestry. SEER‐12 classifies Hispanic ethnicity according to the NAACCR NHIA, which could contain inaccuracies if ethnicity was not reported in the original medical record. 18 However, prior analyses have indicate that the NHIA has high accuracy, sensitivity, and positive predictive value in areas that have both very low and very high Hispanic populations. 36 In addition, the study had no access to information on country of birth.
The current study demonstrates that TGCT incidence is increasing overall in the United States, but the increases are more pronounced among populations other than NHW men, who have historically had the highest rates. Future studies should aim to investigate the risk factors associated with differences between race/ethnic groups and, for Hispanic men in particular, differences in histology patterns.
AUTHOR CONTRIBUTIONS
Andrea A. Almeida: Investigation and writing–original draft. Aika Wojt: Formal analysis and writing–review and editing. Catherine Metayer: Writing–review and editing. Peter A. Kanetsky: Writing–review and editing. Barry I. Graubard: Methodology and writing–review and editing. Christian S. Alvarez: Methodology and writing–review and editing. Katherine A. McGlynn: Conceptualization, methodology, and writing–review and editing.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Supporting information
Supplementary Material
ACKNOWLEDGMENTS
This work was supported by the National Institutes of Health Intramural Research Program, National Cancer Institute. The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views, opinions or policies of the Uniformed Services University of the Health Sciences; the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.; the Department of Defense; or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the US Government.
Almeida AA, Wojt A, Metayer C, et al. Racial/ethnic differences in trends of testicular germ cell tumor incidence in the United States, 1992–2021. Cancer. 2025;e35706. doi: 10.1002/cncr.35706
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are openly available from the Surveillance, Epidemiology and End Results Program at https://seer.cancer.gov.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Material
Data Availability Statement
The data that support the findings of this study are openly available from the Surveillance, Epidemiology and End Results Program at https://seer.cancer.gov.