Testicular Cancer Incidence and Mortality Within Rural and Urban Regions

Abstract

Purpose:

Testicular cancer (TCa) is among the most common cancers within adolescent and young adult (AYA) male populations. However, information is limited to variations in incidence and mortality outside of racial/ethnic subgroups. Rural regions historically have a greater overall cancer incidence than urban regions, although some key differences exist regarding site. TCa-specific incidence and mortality disparities are not commonly reported in this context. This study aims to help fill that gap by providing discovery evidence if there is an association between US rural/urban regions and TCa incidence and mortality.

Methods:

Secondary analysis of Surveillance, Epidemiology, and End Results incidence and mortality data were employed to determine if rural/urban TCa incidence and mortality disparities exist among U.S. males.

Results:

There was a 2.6% increased rate of TCa in U.S. urban as compared with rural geographic regions from 2011 to 2015. When geographic region is disaggregated, rural regions see higher rates than urban. When factoring in race/ethnicity, White/Caucasians and Hispanics had statistically higher urban rates whereas American Indian/Alaskan Natives and Asian/Pacific Islander groups had statistically higher rural rates.

Conclusion:

Geographic regional TCa variation research is virtually nonexistent for U.S. males, specifically AYAs of color. Determining preliminary trends in rural and urban regions can assist in the creation of more targeted services, particularly among underserved and vulnerable populations that have tenuous access to health care, to reduce disparate health outcomes. Exploring geographic differences in TCa incidence and mortality can have implications within service industry, health care accessibility, and public health justice areas of research and outreach.

Background

Testicular cancer incidence and mortality

Testicular cancer (TCa) is the most common malignancy among males 15–45 years of age, with the majority of the cases affecting 15–34-year-old adolescent and young adult (AYA) White/Caucasian males.¹ TCa incidence has doubled during the past 40+ years with variations in occurrence across the globe.^2–6 For example, the analysis of Nigam et al. on Surveillance, Epidemiology, and End Results (SEER) 13 and EUREG data highlighted that between 1992 and 2002, 15 of the 19 European countries included in the study had rising rates of incidence. Between 1992 and 2009, the United States' age-standardized TCa incidence rate increased from 5.7/100,000 to 6.8/100,000.⁷

Within-region rates are not homogenous.³ For example, the incidence rate for Nordic countries (the nations with the highest TCa rates in the world) varied greatly. Norway and Denmark had the two highest incidence rates of any country studied (9.6/100,000 and 9.2/100,000, respectively). Sweden and Finland, on the other hand, had incidence rates of 5.3/100,000 and 3.7/100,000, respectively. Similar differences were observed in other areas, particularly among select Global South regions where, historically, testis cancer is even more of a rarity.

TCa mortality rates have decreased since the introduction of cisplatin-based chemotherapy in the late 1970s/early 1980s.^4,8,9 However, not all populations have equitable access to the gold standard treatment, thus helping create disparate outcomes. For example, a marked difference with rates of the Global South is that although incidence is lower when compared with Western nations, mortality rates trend higher.³ Similarities can be seen within nations, such as the disparities between U.S. White/Caucasians and historically marginalized populations.

Incidence and mortality by race and ethnicity in the United States

Ghazarian et al.¹⁰ notes that four out of the five major racial/ethnic groups saw increasing incidence rates from the early to mid-1990s to 2011. The authors further state that Hispanics had the largest annual percentage change (APC) of 2.94, followed by Black/African American (1.67), White/Caucasian (1.23), and Asian/Pacific Islander (1.04).¹⁰ From 1992 to 2010, the APC among Hispanics was 3.61 while among non-Hispanics was 1.04. From 2000 to 2010, those APCs were 3.81 for Hispanics and no trend for non-Hispanics.¹¹ According to some estimates, Hispanics will have the greatest incidence rate of TCa of any ethnicity in the United States by the year 2026.¹²

Although there has been a substantial decrease in mortality rates for most populations, the success of TCa treatment has not been shared by all.^2,8 Although TCa is very curable, a diagnosis of distant-stage disease is more ominous and is associated with lower survival rates than a local stage diagnosis. Minority populations are 1.6 times more likely to die from the disease as compared with their White/Caucasian counterparts.¹³ The proportion of cases with a distant-stage diagnosis was much greater in Hispanics (16.1%) and Black/African Americans (13.8%) when compared with White/Caucasians (9.6%). American Indians/Alaska Natives and Asian/Pacific Islanders showed an even greater proportion of late-stage diagnosis at 16.8% and 14.9%, respectively.¹⁴ When compared with White/Caucasians, Black/African Americans had a 127% increased TCa mortality risk in the first 10 years postdiagnosis. Stage at presentation was deemed the most significant factor in the survival rate disparity.¹⁵

There are signals, however, that the TCa survival disparity between White/Caucasians and minority male populations may be closing. From 1983 to 2011, minority males' overall 10-year survival rate increased from 84% to 86%, whereas White/Caucasians remained steady, hovering around 88%–89%. Cancer-specific survival rates also improved for minority males (rising 88%–91%) compared with White/Caucasians, which decreased from 94% to 93%.¹³

TCa in urban and rural environments

A recent trend in the literature focuses on the rural and urban divide with the discussion revolving around access to health care concerns or differing exposures between geographic regions.^16–18 For example, those residing in a rural region were less likely to receive screening services and dental visits¹⁶ and have a greater rate of ambulatory care-sensitive hospitalizations then their more urban counterparts.¹⁷ Pertaining to cancer, generally, nonmetropolitan populations had a greater overall cancer incidence (460/100,000) than metropolitan populations (447/100,000),¹⁸ although some key differences exist regarding cancer site.

It is worth noting that the terms urban and rural differ globally. The U.S. Census defines urban as a settlement of at least 2500 people and an urbanized area as 50,000+ people.¹⁹ However, this varies globally with more urbanized countries (i.e., Japan) having higher thresholds for urban than more rural countries (i.e., Iceland).

TCa-specific disparities are not commonly discussed within a rural–urban context. Those studies reporting on the matter, however, demonstrate a trend toward increasing urban TCa rates compared with rural. Dutch reports highlight a shift from rural-dominated to a leveling out of rates between the 1960s to the 2000s.^20,21 French urban and rural incidence rates both rose in the past two decades but urban saw higher rates than rural in overall cases. Swiss rates are trending higher in urban areas than rural for the total male population and 15–54 age-specific population.²² Recent research indicated that a greater level of urbanization in China was associated with increased rates of TCa, as well as testicular dysgenesis syndrome.^23,24 Although seemingly linked in etiology, some research suggests an unknown environmental factor as responsible for the rapid rise in TDS-related symptoms.²⁵

Considering the dynamism in recent TCa incidence rates and disparate mortality outcomes between demographic groups in the United States, it is imperative to investigate other metrics to shed further light on existing health inequities. Although trends in the literature investigate if rural or urban regions are more affected by TCa globally, related research is virtually nonexistent for U.S. males, specifically AYAs of color. Therefore, this study aimed to provide preliminary evidence on existing TCa health disparities with specific emphases of rural/urban geographic regions and race/ethnic identity.

Determining preliminary trends in rural and urban regions can assist in the creation of more targeted services to reduce disparate health outcomes among marginalized populations. Exploring geographic differences in TCa incidence and mortality can have implications within service industry, health care accessibility, and public health justice areas of research and outreach.

Methods

A secondary data analysis aimed to determine if rural/urban TCa incidence and mortality disparities exist among U.S. males in an attempt to fill in this apparent gap in the literature. A secondary focus of the analysis aimed to expand further upon possible racial/ethnic disparities in TCa outcome metrics.

This study gathered incidence and mortality data from the SEER program run by the National Cancer Institute (NCI). SEER comprises 17 population-based tumor registries and encompasses 28% of the United States population. Virtually 100% of cancer cases are represented within each registry. This study utilized SEER*Stat 8.3.5 to calculate the age-adjusted incidence rates, rate ratios, and trends for TCa in rural and urban environments. Incidence and mortality rates were obtained as a 5-year average from 2011 to 2015 utilizing Tiwari modifications. Incidence trends were analyzed from 2000 to 2015, and the APC and total change was calculated. Rate ratios with p values ≤0.05 indicated statistically significant differences between rural and urban populations. APCs with p values ≤0.05 indicated nonzero changes in incidence rates.

The SEER mortality function was used to analyze mortality differences between rural and urban geographic regions. Data were aggregated by county. The information was obtained through an NCHS database that SEER later gained access to. Due to the heterogeneity in the operationalization process of primary variables, the population sampled is much larger and puts more restrictions on race identification than in original SEER databases. For example, only the racial/ethnic groups “White, Black, and Other” were identified.

Rural and urban populations were defined according to the 2013 Rural/Urban Continuum Code (RUCC) definitions. Urban was defined as codes 1 through 3. Rural was defined as codes 4 through 9. Clemons et al.²⁶ was used to help guide the operationalization of rurality and urbanity.

International Classification of Disease Oncology-3 (ICD-O-3) histological codes were used in this analysis to differentiate seminomas from nonseminomas. Seminomas were defined using ICD-O-3 codes 9061 and 9063. Stage at diagnosis was identified based on the American Joint Committee on Cancer's (AJCC) criteria 1 through 3. Regions were defined according to the United States census regions: West, Midwest, Northeast, and South.

Results

Incidence

There was a 2.6% increased rate of TCa in the United States urban as compared with rural geographic regions from 2011 to 2015 (Table 1). When geographic region is disaggregated, rural regions saw higher rates than urban. The rural Northeast U.S. had the highest disparity (∼20% increased rate) among all four regions compared with their urban counterpart. However, these rates are not significant at the p ≤ 0.05 critical value.

Table 1.

2011–2015 Incidence of Testicular Cancer in the United States by Region in Rural and Urban Populations

	Rural	Urban	Rate ratio	p
All	5.6	5.8	1.026	>0.05
West	6.4	6	0.9365	>0.05
Midwest	6.8	6.1	0.9003	>0.05
Northeast	7.5	6	0.8021	>0.05
South	4.8	4.5	0.9535	>0.05

Rates are per 100,000 and age adjusted to the 2000 United States Std Population (19 age groups—Census P25-1130) standard; confidence intervals (Tiwari mod) are 95% for rates and ratios.

When factoring in race and ethnicity, statistically significant differences in rural and urban incidence rates were present among White/Caucasian, American Indian/Alaskan Native, Asian/Pacific Islander, and all-race/ethnicity Hispanics (all Hispanics) (Table 2). The rates of White/Caucasians and all Hispanics were higher in urban regions (16.1% and 32.5%, respectively), whereas rates for American Indian/Alaskan Natives and Asian/Pacific Islanders were higher in rural regions (62.1% and 45.7%, respectively) as compared with their geographic counterparts. Black/African Americans and non-White Hispanics did not have significant differences between rural and urban geographic regions.

Table 2.

2011–2015 Incidence of Testicular Cancer in the United States by Ethnicity in Rural and Urban Populations

	Rural	Urban	Rate ratio	p
All	5.6	5.6	1.0139	>0.05
White/Caucasian	6.4	7.4^a	1.1611	<0.05
Black/African American	1.8	1.6	0.8477	>0.05
American Indian/Alaskan Native	7.3	2.8^a	0.3791	<0.05
Asian/Pacific Islander	4.1	2.2^a	0.5428	<0.05
All Hispanic	4.1	5.4^a	1.3247	<0.05
Non-White Hispanic	1.2	2.6	2.148	>0.05

Rates are per 100,000 and age adjusted to the 2000 United States Std Population (19 age groups—Census P25-1130) standard; confidence intervals (Tiwari mod) are 95% for rates and ratios.

The rate ratio indicates that the rate is significantly different than the rate for rural (p < 0.05).

Regarding staging of TCa (i.e., Stages 1, 2, and 3), only Stage 2 demonstrated statically significant differences between rural and urban geographic regions where urban was higher than rural by ∼25% (Table 3). In terms of seminoma versus nonseminoma, there were no statistically significant differences between rural and urban geographic regions (Table 4).

Table 3.

2011–2015 Incidence of Testicular Cancer in the United States by Stage in Rural and Urban Populations

	Rural	Urban	Rate ratio	p
1	3.8	3.9	1.0177	>0.05
2	0.6	0.7^a	1.2466	<0.05
3	0.8	0.7	0.9407	>0.05

Rates are per 100,000 and age adjusted to the 2000 United States Std Population (19 age groups—Census P25-1130) standard; confidence intervals (Tiwari mod) are 95% for rates and ratios.

The rate ratio indicates that the rate is significantly different than the rate for rural (p < 0.05).

Table 4.

2011–2015 Incidence of Testicular Cancer in the United States by Seminoma or Nonseminoma in Rural and Urban Populations

	Rural	Urban	Rate ratio	p
Seminoma	3	3.1	1.0379	>0.05
Nonseminoma	2.6	2.7	1.0124	>0.05

Rates are per 100,000 and age adjusted to the 2000 United States Std Population (19 age groups—Census P25-1130) standard; confidence intervals (Tiwari mod) are 95% for rates and ratios.

Mortality

Racial mortality analyses were limited as there were fewer than 10 deaths in the rural Black population, thus making reports for that group unavailable. Furthermore, stratification of “Other” yielded similar results to the rural Black population due to low mortality numbers. Analyses indicted no significant difference in TCa mortality between rural and urban populations (Table 5).

Table 5.

2011–2015 Rural/Urban Mortality in Testicular Cancer (Men)

	Count	Rate	Rate ratio	p
Rural	316	0.3
Urban	1618	0.2	0.8908	>0.05

Rates are per 100,000 and age adjusted to the 2000 United States Std Population (19 age groups—Census P25-1130) standard; confidence intervals (Tiwari mod) are 95% for rates and ratios. Underlying mortality data provided by NCHS.

Discussion

Demographically aggregated samples did not demonstrate statistically significant differences between geographic regions (both in the aggregate and as specific subregions [i.e., West, Midwest, Northeast, and South]). However, the trend for each disaggregated geographic region was that rural had higher rates than urban areas. This stands in contrast to the recent literature illustrating a global shift from rural to urban dominance for TCa incidence.

While it is historically expected that White/Caucasian populations would have one of, if not the, highest TCa incidence, there were some interesting findings regarding TCa manifestation within racial/ethnic groups, particularly within the context of rural and urban geography. Statistically significant differences within racial/ethnic groups were seen between White/Caucasians, American Indian/Alaskan Natives, Asian/Pacific Islander, and all Hispanics rural and urban populations. White/Caucasians and all Hispanics had statistically higher urban rates, whereas American Indian/Alaskan Natives and Asian/Pacific Islander groups had statistically higher rural rates.

White/Caucasians had the highest rates among urban regions while having the second highest rate in rural regions. Among rural populations, American Indian/Alaskan Natives had the highest rates among all racial/ethnic groups. However, this is may be skewed by the relatively small rural American Indian/Alaskan Native population size. Black/African Americans and non-White Hispanics had the lowest rural rates of any demographic group, which is consistent with the urbanization and suburbanization trends of these populations during the past half-century²⁷ (i.e., lessening overall numbers in rural areas), which would severely curtail the incident cases in the rural regions of the United States.

Of particular interest was the dramatic decrease in American Indian/Alaskan Natives TCa incidence when comparing rural (7.3/100,000) to urban (2.8/100,000). American Indian/Alaskan Natives have historically displayed geographical variations in behavioral risk factors such as adverse dietary, cigarette smoking, and binge drinking tendencies, among several others,²⁸ which may explain the observed differences in TCa incidence. Geographical differences can be seen in other cancer diagnoses within this population, such as colorectal cancer and cervical cancer.²⁹ Data presented in these analyses support other's work in terms of TCa incidence among American Indian/Alaskan Native populations.⁵

American Indian/Alaskan Natives secluded to specific communities present an inherent public health challenge. Rural communities of this demographic are not uniformly affected by the same health disparities and are often isolated from one another. Dependent on cultural and environmental factors, there could be substantial differences between communities regarding risk factors for TCa. Although the current analysis did not specify which rural regions reflected the highest TCa incidence, additional research should further define the epidemiologic trend of TCa in American Indian/Alaskan Natives within these secluded rural regions.

Similar to American Indian/Alaskan Natives, Asian/Pacific Islanders have significantly higher TCa incidence in rural regions compared with urban regions. We speculate this trend may arise from two underlying factors: (1) rural, environmental risk factors, and (2) high sexually transmitted infection (STI) prevalence, coupled with low urogenital health resource density. First, Asian/Pacific Islander populations in rural areas may experience higher TCa incidence due to environmental risk factors that promote TCa development. Although this is speculative at this moment in the body of research, this would seem consistent with other minority groups within this study reflecting higher incidence rates in rural regions.

Second, and more specific to Asian/Pacific Islanders, increased TCa incidence in rural regions may rise from high STI incidence among Asian/Pacific Islander men, coupled with low urogenital health care service density. Asian/Pacific Islanders, in general, suffer from higher prevalence of STIs, such as gonorrhea, chlamydia, and syphilis, in comparison to the non-Hispanic White majority.³⁰ Notably, research has yet to pinpoint if such diseases directly increase risk of TCa; however, complications stemming from such STIs, if left untreated, such as epididymitis, orchitis, among others, have been associated with increased risk of TCa.^31,32 Asian/Pacific Islander men within rural communities that experience high STI prevalence, but lack the necessary health care resources (e.g., urologists, family planning services, etc.) to address such diseases (AYA males, particularly) may be at higher risk of advanced urogenital sequela if infected, which may increase the risk of TCa in rare cases. This may, to a degree, explain the higher incidence rate in urban regions. Further investigation is needed to formally test this hypothesis.

White/Caucasians and all Hispanics had statistically significant increases in TCa incidence comparing rural to urban geographic regions. One item of note was that non-White Hispanics did not see the same significant trend as all Hispanics, which suggests that the Hispanic population who also identifies as White may be driving the significant trend in rising rates between rural and urban regions.

In terms of staging, only populations diagnosed at Stage 2 showed any significant change in incidence (i.e., a rise in incidence from rural to urban). One reason could be that the urban population has increased access to health care and information about testicular self-examination. However plausible, this needs to be fleshed out further by future research. Further, we chose to look at possible seminoma and nonseminoma cases per geographic region as the different manifestations of the disease impacts the type of treatment needed. Having seminoma or nonseminoma more prevalent in a particular region would have implications for access to health care needs and treatment availability. However, these results were not significant.

Mortality analyses indicated little difference between rural and urban geographic regions. This is most likely due to the effectiveness of treatment options that have been well studied and implemented in the last 40+ years.³³ There tends to be minor variations in metastatic TCa treatment protocols, which provide good 5-year survival rates regardless of rural or urban residence.

Limitations and future directions

Some limitations were unavoidable for our analytical purposes. Mortality rate comparisons were particularly limited in scope due to statistical power limitations. Furthermore, the low number of mortality in most of the demographic subgroups curtailed detailed analytical testing.

Another concern within the datasets was possible misclassification bias. American Indian/Alaskan Native regional distortions could be the result of misclassification bias, which supports assertions that researchers need to be aware of the presence of this type of systematic error.^34,35 Furthermore, errors in data linkage between the Indian Health Service and other national registries (i.e., SEER) present the possibility of regional error. It is possible self-misclassification of race/ethnicity is more prevalent in urban regions, as opposed to rural—more homogenous—populations, which confine most tribal American Indian/Alaskan Native communities. This, however, would not explain the drastic differences in TCa incidence between rural and urban regions in the current analysis.

TCa incidence disparities between American Indian/Alaskan Native rural and urban communities were remarkably large. Further research is needed to discuss the role of both behavioral, environmental, and potential epigenetic factors as risk factors of TCa in rural communities of all racial/ethnic groups, which are also at risk of being misclassified.

One other area of concern is misclassification regarding rural and urban residence. Although rural and urban designation is measured on a spectrum, the variance of urbanity and rurality provide the option for future research to look at more suburban, or even exurban, environments. However, as mentioned before, statistical power concerns are then raised due to the low number of incidence and mortality of TCa.

Finally, the SEER dataset may select for better-quality urban data. A review of 27,938 patients with TCa from 1978 to 2006 indicated that nearly 90% resided in urban areas.³⁶

Conclusion

There are differences in TCa incidence among select demographic populations within specific geographic regions. Reasons for these differences are speculative, but remain essential to identify to inform future research efforts. Moving forward, research needs to define what behavioral, environmental, and/or epigenetic risk factors are present within minority rural communities, particularly YA populations, reflecting higher incidence, as well as to what degree inequities in health care access may affect TCa outcomes and risk.

Footnotes

Acknowledgments

The authors would to thank the researchers at the Behavioral Health Research Group at the University of Central Florida, the Testicular Cancer Society, and Southern Illinois University for their contributions to this ongoing project. Furthermore, this project followed the ethics guidelines set forth in the Declaration of Helsinki and all other precedent ethics statements.

Disclaimer

This study gathered incidence and mortality data from the Surveillance, Epidemiology, and End Results (SEER) program run by the National Cancer Institute (NCI). Rural and urban populations were defined according to the 2013 Rural/Urban Continuum Code (RUCC) definitions. Mortality information was obtained through a National Center for Health Statistics (NCHS) database.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

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