Introduction: Since 2003, using the Surveillance, Epidemiology, and End Results (SEER) database, epidemiological aspects of uveal melanoma have been reported. The aim of this study was to update trends in incidence, treatment, and survival of uveal melanoma in the USA from 1975 to 2020. Methods: Patients were identified using International Classification of Disease for Oncology codes: C69.3 [choroid], C69.4 [ciliary body and iris], and C69.2 [retina]. Trends in age-adjusted incidence, treatment (surgery or radiation), and 5-year relative survival were calculated. Results: A total of 5,563 cases of uveal melanoma were identified. The majority (97%) were reported by hospital inpatient/outpatient clinics. Microscopic (histopathologic or cytologic) confirmation was available in 61%. The mean age-adjusted incidence was 5.6 per million (95% CI: 5.5–5.7). As previously noted, a small but statistically significant (p < 0.05) annual percentage change of 0.5% was detected in whites. The previously reported declining trend in the number of patients treated with surgery alone (93% from 1975 to 1977 vs. 21% from 2017 to 2020) ensued, with ongoing corresponding increasing rates of radiation as the primary treatment (1% from 1975 to 1977 vs. 58% from 2017 to 2020). No change in the 5-year relative survival (82.8%) was observed (reported from 1975 to 2016). Conclusions: Previously reported overall age-adjusted incidence of uveal melanoma is stable throughout the years, with a minor increase in incidence in whites. Treatment trend toward radiation has not led to improvement in survival.

Annual update on national cancer status is reported based upon Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI) [1] as an authoritative source of cancer-related statistics in the United States (US). The data cover 48% of the US population [2]. Since 2003, previously available SEER database-derived results have provided 5-year updates regarding the incidence and trends in treatment and survival in uveal melanoma cases [3‒5]. In this manuscript, we provide current trends in age-adjusted incidence, treatment, and survival in uveal melanoma patients included in the SEER Program database from 1975 to 2020.

Similar to previous reports [3‒5], the National Cancer Institute SEER database file was accessed and analyzed via the SEER*Stat software (version 8.4.3, January 18, 2024) in client-server mode. This software provided all needed tools to calculate age-adjusted incidence and 5-year relative survival of uveal melanoma and trends in treatment [6]. SEER cancer statistics are collected according to the place of an individual’s residence, thus avoiding potential geographic data collection bias from large referral centers. The source SEER data that support the findings of this study are publicly available [2]. Data related specifically for uveal melanoma for this study were extracted by the authors and are not publicly available due to strict privacy, security, and ethical standards but are available upon request from the corresponding author. Our study is IRB exempt as it is based on publicly available anonymized dataset.

Incidence was calculated using a two-step process: first, age-specific rates were determined utilizing census estimates for the US population and the 45-year period of time studied, adjusting for population increases. Second, age-specific rates were then age adjusted to a “standard” population and expressed per million population. We followed the lead of the National Cancer Institute (NCI), which currently reports statistics by adjusting to the US population in the year 2000, correcting for fluctuations in age distribution of the population over time. Age was truncated at 90 years but was available for younger patients.

The updated SEER database currently includes 22 cancer registries; nonetheless, statistics for this study were calculated only from the core 8 SEER registries with data present since 1975, to achieve this kind of longitudinal analysis. The purpose of this careful selection was to avoid bias arising from including newer centers lacking statistical data from the earlier time period.

Cases of ocular and adnexal melanoma were identified using the International Classification of Disease for Oncology (ICD-O-2) codes for both morphology (melanoma: 8,720–8,790) and site (eye and adnexa: C69.0–C69.9) [7]. The subset of primary uveal melanoma was further identified by site: choroid, ciliary body, iris, and “retina” (C69.2–C69.4). A total of 1% of ocular melanoma were coded as arising from the “retina,” which is an exceptionally rare site for primary melanoma [8]. As “retinal melanoma” most likely represented miscoding of uveal melanoma, these cases were included in the analysis. Ocular melanoma coded as “site nonspecific” was excluded. Due to incomplete or lacked uniformity, specific information relating to tumor size was not analyzed.

For incidence, the 95% confidence interval (CI) was calculated using the method developed by Chiang [9]. For analysis of treatment selection, individuals were grouped based upon primary therapy (surgery or radiation). Overall trends in the number of patients treated with surgery alone, radiation alone, both, or unknown/no treatment were determined.

Similar to the previous reports, data regarding specific treatment modality (such as plaque brachytherapy vs. proton beam irradiation) are only available from 1987 onward in various forms and are inconvenient to interpret. Therefore, we omitted these specific data from this analysis with the intention to extend the previous reports, analyzing overall longitudinal trends of the past and present.

For analysis of survival, relative survival rates were used. No adjustment was made using the death certificate “cause of death.” Relative survival is defined as the ratio of the proportion of observed survivors in a cohort of cancer patients to the proportion of expected survivors in a comparable set of cancer-free individuals. The 5-year relative survival was determined for each 3-year time interval between 1975 and 2020, except for the last interval (2017–2020), which was unavailable. Survival calculations were made using the life table method and US census life-expectancy tables for gender and age [10].

During the 45-year time period between 1975 and 2020, there were a total of 6,583 cases of melanoma identified from the SEER database as arising from the eye and the ocular adnexa. A total of 5,563 (84.5%) of these were primary uveal melanoma (site coded as choroid, ciliary body, iris or “retina”). Overall, 682 cases (10.4%) of melanoma were arising from sites including the conjunctiva, cornea, orbit, lacrimal gland, or other overlapping categories. Non-specified site included 338 cases (5.1%), which were excluded from further analysis (Table 1). Rate of primary uveal melanoma in males (52%) was similar to females (48%). Median age at diagnosis was 63 years (range: 5–90 years). Laterality was similar between right eye (49%) and left eye (49%) with small rate unknown (1.4%). A total of 98% of cases of uveal melanoma were in the white race, with only 0.6% of reported cases in the black population, and in the remaining 1.8%, race was unknown. Of special notice, no prior malignancy was reported in almost 87% of the individuals, while 13% had a history of cancer, preceding the diagnosis of uveal melanoma (Table 2). Overall, hospital inpatient units or hospital-based outpatient clinic reported cases were the largest portion (97%), being slightly lower in the last 15 years of the analysis (94.9%) with other hospital outpatient unit or surgery center slightly higher than previous years (2.9%). In 61% of cases, diagnosis was confirmed microscopically (histopathologic or cytologic) (Table 3).

Table 1.

Uveal melanoma from 1975 to 2020: site and morphology

SiteFrequency, nOverall, %1975–1989, %1990–2004, %2005–2020, %
C69.0: conjunctiva 453 6.9 4.9 7.2 7.8 
C69.1: cornea, NOS 30 0.5 0.4 0.8 0.2 
C69.2: retina 64 1.0 1.6 1.1 0.6 
C69.3: choroid 4,695 71.3 63.9 69.2 76.7 
C69.4: ciliary body 804 12.2 16.6 12.4 9.7 
C69.5: lacrimal gland 0.1 0.1 0.1 0.1 
C69.6: orbit, NOS 74 1.1 1.6 0.8 1.1 
C69.8: overlapping lesion of eye and adnexa 120 1.8 2.9 2.6 0.8 
C69.9: eye, NOS 338 5.1 8.0 6.1 3.0 
Total 6,583 100.0 100.0 100.0 100.0 
SiteFrequency, nOverall, %1975–1989, %1990–2004, %2005–2020, %
C69.0: conjunctiva 453 6.9 4.9 7.2 7.8 
C69.1: cornea, NOS 30 0.5 0.4 0.8 0.2 
C69.2: retina 64 1.0 1.6 1.1 0.6 
C69.3: choroid 4,695 71.3 63.9 69.2 76.7 
C69.4: ciliary body 804 12.2 16.6 12.4 9.7 
C69.5: lacrimal gland 0.1 0.1 0.1 0.1 
C69.6: orbit, NOS 74 1.1 1.6 0.8 1.1 
C69.8: overlapping lesion of eye and adnexa 120 1.8 2.9 2.6 0.8 
C69.9: eye, NOS 338 5.1 8.0 6.1 3.0 
Total 6,583 100.0 100.0 100.0 100.0 

All ocular melanomas were identified by site and morphology. Retina, choroid, and ciliary body tumors were uveal melanoma (N = 5,563).

Table 2.

Demographics: uveal melanomas

CharacteristicN = 5,563
Gender, n (%) 
 Female 2,692 (48) 
 Male 2,871 (52) 
Age at diagnosis, years 
 Range 5–90+ 
 Median [IQR] 63 [52, 72] 
Laterality, n (%) 
 Left eye 2,746 (49) 
 Right eye 2,741 (49) 
 Unknown 76 (1.4) 
Race, n (%) 
 White 5,426 (98) 
 Black 35 (0.6) 
 Other/unknown 102 (1.8) 
Prior malignancy, n (%) 
 Present 731 (13) 
 Absent 4,832 (87) 
Microscopic confirmation, n (%) 
 Yes 3,391 (61) 
 No 2,107 (38) 
 Unknown 65 (1.2) 
CharacteristicN = 5,563
Gender, n (%) 
 Female 2,692 (48) 
 Male 2,871 (52) 
Age at diagnosis, years 
 Range 5–90+ 
 Median [IQR] 63 [52, 72] 
Laterality, n (%) 
 Left eye 2,746 (49) 
 Right eye 2,741 (49) 
 Unknown 76 (1.4) 
Race, n (%) 
 White 5,426 (98) 
 Black 35 (0.6) 
 Other/unknown 102 (1.8) 
Prior malignancy, n (%) 
 Present 731 (13) 
 Absent 4,832 (87) 
Microscopic confirmation, n (%) 
 Yes 3,391 (61) 
 No 2,107 (38) 
 Unknown 65 (1.2) 
Table 3.

Uveal melanoma, 1975–2020: reporting distribution

Reporting sourceFrequency, nOverall, %1975–1989, %1990–2004, %2005–2020, %
Hospital inpatient/outpatient or clinic 5,397 97.0 99.3 98.5 94.9 
Radiation treatment or medical oncology center (2006+) 18 0.3 0.0 0.0 0.7 
Laboratory only (hospital or private) 41 0.7 0.2 0.7 1.0 
Physician office/private medical practitioner (LMD) 32 0.6 0.4 0.8 0.5 
Nursing/convalescent home/hospice 0.0 0.1 0.0 0.0 
Other hospital outpatient unit or surgery center (2006+) 74 1.3 0.0 0.0 2.9 
Total 5,563 100.0 100.0 100.0 100.0 
Reporting sourceFrequency, nOverall, %1975–1989, %1990–2004, %2005–2020, %
Hospital inpatient/outpatient or clinic 5,397 97.0 99.3 98.5 94.9 
Radiation treatment or medical oncology center (2006+) 18 0.3 0.0 0.0 0.7 
Laboratory only (hospital or private) 41 0.7 0.2 0.7 1.0 
Physician office/private medical practitioner (LMD) 32 0.6 0.4 0.8 0.5 
Nursing/convalescent home/hospice 0.0 0.1 0.0 0.0 
Other hospital outpatient unit or surgery center (2006+) 74 1.3 0.0 0.0 2.9 
Total 5,563 100.0 100.0 100.0 100.0 

Retina, choroid, and ciliary body tumors were uveal melanoma.

The overall mean age-adjusted incidence of primary uveal melanoma in the US over the 45-year period from 1975 to 2020 was 5.6 per million population (95% CI: 5.5–5.7). Males had a significantly higher age-adjusted incidence of 6.3 per million population (95% CI: 6.1–6.6) compared to females with average age-adjusted incidence of 5.0 (95% CI: 4.8–5.2). The overall age-adjusted incidence of uveal melanoma remained relatively stable between 1975 and 2020 (Fig. 1). Nonetheless, standardizing the data by race to take into account population-based changes in racial proportions, a small but statistically significant (p < 0.05) annual percentage change (APC) of 0.5% was detected only in whites (Fig. 2).

Fig. 1.

Age-adjusted incidence of uveal melanoma (1975–2020), expressed as the rate per million adjusted to the 2000 US population (uveal melanoma cases only).

Fig. 1.

Age-adjusted incidence of uveal melanoma (1975–2020), expressed as the rate per million adjusted to the 2000 US population (uveal melanoma cases only).

Close modal
Fig. 2.

Age-adjusted incidence of uveal melanoma (1975–2020) among whites, expressed as the rate per million adjusted to the 2000 US population (uveal melanoma cases only). Among whites, the rate was 6.7 per million (95% CI: 6.5–6.9), and there was a small, but statistically significant trend in the percentage change of 0.5 (95% CI: 0.2–0.7%; p < 0.05).

Fig. 2.

Age-adjusted incidence of uveal melanoma (1975–2020) among whites, expressed as the rate per million adjusted to the 2000 US population (uveal melanoma cases only). Among whites, the rate was 6.7 per million (95% CI: 6.5–6.9), and there was a small, but statistically significant trend in the percentage change of 0.5 (95% CI: 0.2–0.7%; p < 0.05).

Close modal

Treatment modalities rates between the years 1975 and 2020 showed a progressive decline in the percentage of patients treated with surgery alone (93% from 1975 to 1977 vs. 21% from 2017 to 2020). A correspondent increase in the percentage of patients treated with radiation alone (1% from 1975 to 1977 vs. 58% from 2017 to 2020) was noted. No significant change was observed in the number of cases of uveal melanoma treated with both therapies and with other treatment (Fig. 3). The 5-year relative survival rate (82.8%) remained stable during the period from 1975 to 2016 (5-year follow-up data are not yet available for 2017–2020) (Fig. 4).

Fig. 3.

Trends in treatment of uveal melanoma (1975–2020). Percentage of cases per year treated by each modality (uveal melanoma cases only). There was a decrease in cases treated only by surgery from 93% in 1975–1977 to 21% in 2017–2020. The percentage of cases treated with radiation alone increased from 1% in 1975–1977 to 58% in 2017–2020.

Fig. 3.

Trends in treatment of uveal melanoma (1975–2020). Percentage of cases per year treated by each modality (uveal melanoma cases only). There was a decrease in cases treated only by surgery from 93% in 1975–1977 to 21% in 2017–2020. The percentage of cases treated with radiation alone increased from 1% in 1975–1977 to 58% in 2017–2020.

Close modal
Fig. 4.

Five-year relative survival among uveal melanoma cases from 1975 to 2016. Data for the final time period (2017–2020) were not available and are not reported.

Fig. 4.

Five-year relative survival among uveal melanoma cases from 1975 to 2016. Data for the final time period (2017–2020) were not available and are not reported.

Close modal

Since 2003, using the SEER registries (which represent real-world data of the US population) we have consistently documented incidence, treatment, and survival in patients with uveal melanoma [3‒5]. This report updates using additional recent 5-year data.

Parameters resemble those in the reports: stable incidence of uveal melanoma in the US over 45 years with 5.6 cases per million population, compared to the age-adjusted incidence from 1973 to 1997 (5.0, 95% CI: 4.7–5.4, adjusted to the 2000 US standard population), 1973–2008 (5.1, 95% CI: 4.8–5.3, adjusted to the 2000 US standard population), or 1973–2013 (5.2, 95% CI: 5.0–5.4, adjusted to the 2000 US standard population) [5].

In a comprehensive study of incidence of uveal melanoma (1988–2012) derived from 347 cancer registries worldwide (35 countries), Denmark had the highest incidence of 12.1 cases per million person-years during the 2003–2007 whereas Canada and the US generally displayed age-standardized incidence rates between 6.0 and 7.9 cases per million person-years [11]. Temporal trends in incidence showed that a majority (80%) of countries had stable incidence. Only 7 (20%) countries experienced a change in incidence, represented as average annual percentage change (AAPC). After adjusting for age-cohort effects (Ireland and Sweden), India, Philippines, and Finland exhibited a decrease in incidence, whereas South Korea (AAPC = 1.8, p ≤ 0.05) and Russia (AAPC = 4.9, p ≤ 0.05) experienced an increase [11].

In a nationwide retrospective cohort study that spanned over a 70-year period (1943–2017), the investigators from Denmark linked data from registry-based resources to clinical charts and pathology records of 2,367 patients with posterior uveal melanoma [12]. They observed an overall increase in incidence rate of uveal melanoma (APC of 0.25% [95% CI: 0.08–0.42]) attributable to smaller tumors (AJCC T1 + T2 tumors) rather than larger tumors (AJCC T3 + T4 tumors) [12]. Observed increased incidence may be due to evolving diagnostic criteria to treat smaller tumors, which may include larger nevi as not all cases underwent pathologic confirmation [13].

In the global study, increasing incidence rate did not reach statistical significance for Denmark and US [11]. Narrower coverage in the global study (1988–2012) compared to wider coverage in the Danish study (1947–2017) can possibly explain the differences [11, 12]. For US, we also did not observe any change in incidence between 1975 and 2020. However, when standardizing the data by race accounting for population-based changes in racial proportions in the US, a small but statistically significant (p < 0.05) APC of 0.5% was detected only in whites. Future studies may be able to confirm such a trend.

The portion of cases reported by hospitals was high as in previous reports, although somewhat lower between 2005 and 2020 with a slight rise in the reporting rate from hospital outpatient unit or surgery center. Greater awareness together with implementation of electronic medical records and coding may explain the lower rate of “non-specified” melanoma coding and higher choroidal melanoma coding in the time period between 2005 and 2020.

A rise in globe salvaging radiation treatment through the years was noted, coupled with a decline in surgery rates as primary therapy (mainly enucleation), similar to the previous SEER report [5]. The Collaborative Ocular Melanoma Study (COMS) suggested that plaque brachytherapy was offered as an alternative to enucleation for medium-sized tumors, and these data coincide with this notion. Also consistent with COMS data is the absence of survival advantage in patients undergoing enucleation over brachytherapy, and this analysis shows that radiation has continued to predominate as a primary therapy [14]. In a recent report, racial, ethnic, and socioeconomic status (SES) associations with treatment and survival in uveal melanoma were explored by multivariate analyses of 4,475 individuals derived from the SEER data (January 1, 2004, to December 31, 2014) [15]. Patients who were nonwhite (OR, 1.45; 95% CI: 1.12–1.88) and socioeconomically disadvantaged (lower SES: OR, 2.21; 95% CI: 1.82–2.68) were more likely to receive primary enucleation rather than radiation even though there were no differences in stage at diagnosis between race/ethnicity and SES. Such treatment choice did not adversely influence disease-specific survival, which did not vary significantly by racial/ethnic or SES strata. Several factors could have contributed to treatment choice including but not limited to educational level, distance from specialized centers, and need for long-term ocular surveillance following globe-sparing treatments [15].

Nonetheless, SEER does not capture and therefore cannot offer a meaningful interpretation regarding survival benefits of ocular therapy. Several lines of evidence suggest that the ocular treatment may be palliative [16]. The present report, similar to previous reports, continues to show that the 5-year relative survival (82.8%) during the past 4 decades, from 1973 to 2016, has not changed. The prognostication and differentiation techniques offered in the last decade to identify patients with low and high probability of metastatic disease [17, 18] have not conferred improvement in survival rate. It will be several years before impact of newer systemic therapies for uveal melanoma is captured in SEER database [19‒21].

In summary, SEER database continues to be a reliable and consistent source of longitudinal data for uveal melanoma. The incidence (5.6 per million population) of uveal melanoma and the 5-year relative survival rate (82.8%) have not changed between 1973 and 2020. As improved strategies to treat metastatic disease become established [19], hopefully this trends analysis in the future will demonstrate a triumphant march toward improved higher relative survival rate.

An ethics statement was not required for this study type since no human or animal subjects or materials were used. Our study is IRB exempt as it is based on publicly available anonymized dataset.

A.D.S. is Editor-in-Chief of Ocular Oncology and Pathology and reported financial activities outside the submitted work: Aura Biosciences (consultancy), IsoAid LLC (consultancy), and Castle (consultancy). Other authors have no conflicts of interest to declare.

This work was supported in part by an unrestricted grant from Research to Prevent Blindness to the Cole Eye Institute. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Y.W.: interpretation of the data and drafting and reviewing of the manuscript. J.B.: acquisition and analysis of the data and reviewing and approval of the manuscript for publication. A.D.S.: conception of the manuscript, reviewing and editing of the manuscript, and final approval of the version to be published.

Data related specifically for uveal melanoma for this study were extracted by the authors and are not publicly available due to strict privacy, security, and ethical standards but are available upon request from the corresponding author.

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