Current Issue
Spring/Summer 2025, Vol. 32 No. 1
Hong Kong J. Dermatol. Venereol. (2025) 32, 4-18
Original Article
Joinpoint regression analysis of incidence and mortality rates for superficial spreading malignant melanoma across diverse demographic characteristics and tumour attributes: a 22-year review of superficial spreading malignant melanoma
不同人口特徵與腫瘤屬性的淺表擴散型惡性黑色素瘤發病率與死亡率的連結點回歸分析：淺表擴散型惡性黑色素瘤22年回顧
Abstract
Background: In recent years, the incidence and mortality rates of superficial spreading malignant melanoma (SSMM) have significantly increased. However, comprehensive epidemiological studies examining these trends remain scarce. This study aims to explore changes in SSMM incidence and mortality over Twenty-two years. Methods: Data on SSMM patients were extracted from the SEER database, covering incidence and incidence-based mortality. Joinpoint regression analysis was used to calculate the Average Annual Percent Change (AAPC) and 95% confidence intervals (CI). Results: From 2000 to 2021, 131,235 SSMM cases were identified with an age-adjusted incidence rate of 6.98 (95% CI: 6.94-7.01) and an incidence-based mortality rate of 1.33 (95% CI: 1.31-1.34). Males accounted for 54.92% of cases, with 48.82% of patients under 60 years old. Predominantly, SSMM lesions were found on the limbs (46.64%), scalp and neck (14.9%), and trunk (38.47%). SSMM incidence increased significantly (AAPC=2.1%) throughout the study period, while mortality surged sharply from 2000 to 2012 (AAPC=19.9%) before stabilising. The trends varied by sex, age, race, and primary tumor site, with higher rates observed among older individuals, White patients, and those with tumors in sun-exposed areas. Conclusions: The findings reveal a notable increase in SSMM incidence and mortality, with variations across demographic and clinical subgroups. These insights can enhance our understanding of SSMM and support targeted healthcare interventions.
背景：近年來，淺表擴散型惡性黑色素瘤 (SSMM) 的發病率和死亡率都顯著增加。然而，檢視這些趨勢的全面流行病學研究仍然很少。本研究旨在探討22年來 SSMM 發病率和死亡率的變化。方法：從 SEER 資料庫中擷取 SSMM 患者的資料，涵蓋發病率和以發病率為基礎的死亡率。接合點回歸分析用於計算平均年度百分比變化 (AAPC) 和 95% 置信區間 (CI)。結果：從2000年到2021，共發現131,235例 SSMM 病例，經年齡調整後的發病率為6.98 (95% CI: 6.94-7.01)，發病死亡率為 1.33 (95% CI: 1.31-1.34)。男性佔54.92%，60歲以下的病患佔48.82%。SSMM 病變主要發生在四肢 (46.64%)、頭皮和頸部 (14.9%) 以及軀幹 (38.47%)。在整個研究期間，SSMM 的發病率顯著增加 (AAPC = 2.1%)，而死亡率則在2000 年至2012年間急速上升 (AAPC = 19.9%)，之後趨於穩定。趨勢因性別、年齡、種族和原發腫瘤部位而異，年長者、白人患者和腫瘤位於陽光曝曬部位者的發生率較高。結論：研究結果顯示 SSMM 發病率和死亡率顯著增加，不同人口和臨床次群體的情況也有差異。這些洞察力可增進我們對 SSMM 的了解，並支援有針對性的醫療照護干預措施。
Keywords: Incidence, Mortality, SEER, Superficial spreading malignant melanoma, Trends
關鍵詞: 發病率、死亡率、SEER、表淺擴散性惡性黑色素瘤、趨勢
Introduction
Superficial spreading malignant melanoma (SSMM) represents a highly aggressive form of cutaneous malignancy, predominantly affecting sun-exposed areas of the skin. Characterised by rapid tumour growth, significant potential for metastasis, and irregular pigmented lesions, SSMM exhibits considerable clinical heterogeneity.1,2 As the incidence of melanoma has been rising steadily, therapeutic strategies for SSMM have also evolved. Current treatment modalities primarily encompass surgical excision, immunotherapy, targeted therapy, and radiotherapy,3-5 though their efficacy in enhancing survival and reducing recurrence rates varies markedly.6-9
Epidemiologically, SSMM demonstrates pronounced geographic and demographic disparities in both incidence and mortality rates worldwide. Numerous factors, including age, sex, race, tumour characteristics, diagnostic timing, and lifestyle, contribute to the onset and prognosis of SSMM.5,10-12 A nuanced understanding of the epidemiological trends of SSMM is essential for the formulation of effective prevention and control strategies.
This study employs Joinpoint regression analysis to systematically evaluate the trends in SSMM incidence and mortality over the past 22 years. Despite prior epidemiological studies on melanoma, these investigations are relatively outdated and lack a comprehensive, separate analysis focused specifically on SSMM.13,14 Joinpoint regression is a robust epidemiological tool that identifies significant inflection points within time series data, revealing shifts and acceleration patterns in incidence and mortality rates over time.15,16 Utilising this method to analyse the epidemiological trends of SSMM enables the identification of critical time points, potentially uncovering factors that influence changes in incidence and mortality. This approach is of substantial importance for designing targeted public health interventions, improving patient outcomes, and optimising clinical decision-making.
Materials and methods
Data sources
All data for this study were sourced from the Surveillance, Epidemiology, and End Results (SEER) database.17 Utilising SEERStat software (version 8.4.3), patients diagnosed with superficial spreading melanoma in situ and SSMM were identified. Within the SEERStat "Rate Session", the sub-databases selected were "Incidence - SEER Research Data, 17 Registries, November 2023 Sub (2000-2021)" and "Incidence-Based Mortality - SEER Research Data, 17 Registries, November 2023 Sub (2000-2021)." This database aggregates data from 17 cancer registries, encompassing approximately 26% of the U.S. population, and is renowned for its multi-centre, high-quality, and transparent nature.18 For SSMM, we primarily focused on dermatological cases, employing codes from the International Classification of Diseases for Oncology, 3rd Edition, 2000: 8743/2 (superficial spreading melanoma in situ) and 8743/3 (superficial spreading melanoma, malignant), along with anatomical codes C44.0, C44.1, C44.2, C44.3, C44.4, C44.5, C44.6, C44.7, C44.8, and C44.9. The study included variables such as sex, age at diagnosis/death, race, median household income, rural-urban distribution, primary tumour site, SEER summary stage, and surgery. All variables with missing or incomplete data were excluded. Given that patient identities in the SEER database are anonymised and the data are publicly accessible, neither ethics committee approval nor informed consent was required.
Demographic and tumour characteristics
Age at diagnosis/death was categorised into three groups: <60, 60-69, and ≥70 years. Racial classifications were segmented into White, Black, Asian, and Other (encompassing American Indian, Alaska Native). Median household income (Income) above US$75,000 was considered indicative of high-income groups. Based on geographic distribution, populations were divided into rural and urban. Primary tumour sites were stratified into scalp and neck, trunk, and limbs. The SEER database further stratifies the SEER summary stage (stage) into three distinct categories: localised, regional, and distant.
Statistical analysis
The SEERStat software was utilised to calculate age-adjusted incidence and incidence-based mortality rates, expressed per 100,000 individuals and adjusted to the 2000 US Standard Population (based on 19 age groups from Census P25-1130). Additionally, 95% confidence intervals (CI) for rates and ratios were generated using the SEERStat software according to the Tiwari 2006 modification. The Joinpoint regression program (version 5.2.0) was employed to analyze trends in incidence and incidence-based mortality for SSMM patients. The Annual Percent Change (APC) measures the intrinsic trend for each discrete interval of the segmented function, or the overall trend when no joinpoints are present. The Average Annual Percent Change (AAPC) provides an aggregate assessment of the mean trends across multiple intervals. Statistical significance was determined at p<0.05.19 The Joinpoint regression model, developed by the Division of Cancer Control and Population Sciences at the National Cancer Institute, is widely used in studying trends in cancer incidence and mortality. In 1998, Kim et al16 first introduced the Joinpoint regression model, which establishes segmented regression based on the temporal characteristics of disease distribution. This model divides the study period into distinct intervals through various joinpoints, optimising and fitting trends for each interval, thus allowing for a nuanced evaluation of disease shifts within specific segments of the overall timeframe.
Result
In this analysis, a total of 131,235 SSMM patients were included, with a higher proportion being male (72,070, 54.92%) and primarily of white ethnicity (123,073, 99.09%). For detailed information, see Table 1. The age distribution shows that a significant portion were aged 60 and above, with 28.2% aged over 70 years. Most patients resided in urban areas (109,394, 86.48%), and over half reported a median household income of US$75,000 or more (73,332, 57.84%).
| Table 1 SSMM incidence and incidence-based mortality (2000-2021) | ||||
|---|---|---|---|---|
| Variables | Incidence Counts, No. (%) | Age-Adjust-Rate (95% CI) | Incidence-Based Mortality Counts, No. (%) | Age-Adjust-Rate (95% CI) |
| Overall | 131235 (100) | 6.98 (6.94-7.01) | 24520 (100) | 1.33 (1.31-1.34) |
| Sex | ||||
| Male | 72070 (54.92) | 8.29 (8.23-8.35) | 16489 (67.25) | 2.24 (2.21-2.28) |
| Female | 59165 (45.08) | 6.09 (6.04-6.14) | 8031 (32.75) | 0.73 (0.72-0.75) |
| Age at Diagnosis/Death (y) | ||||
| ＜60 | 64071 (48.82) | 4.16 (4.13-4.19) | 4713 (19.22) | 0.24 (0.23-0.24) |
| 60-69 | 30160 (22.98) | 18.5 (18.29-18.71) | 4921 (20.07) | 0.27 (0.26-0.27) |
| ≥70 | 37004 (28.2) | 23.36 (23.12-23.6) | 14886 (60.71) | 0.83 (0.81-0.84) |
| Race | ||||
| White | 123073 (99.09) | 8.36 (8.32-8.41) | 24192 (99.04) | 1.6 (1.58-1.62) |
| Black | 238 (0.19) | 0.13 (0.12-0.15) | 67 (0.27) | 0.05 (0.04-0.06) |
| Asian | 592 (0.48) | 0.3 (0.28-0.33) | 120 (0.49) | 0.07 (0.06-0.08) |
| Other | 304 (0.24) | 1.36 (1.2-1.53) | 48 (0.2) | 0.3 (0.21-0.4) |
| Median Household Income | ||||
| ≥75,000 | 73332 (57.84) | 7.07 (7.01-7.12) | 10899 (44.43) | 1.32 (1.3-1.35) |
| <75,000 | 53453 (42.16) | 6.34 (6.28-6.39) | 13632 (55.57) | 1.33 (1.31-1.35) |
| Rural-Urban Distribution | ||||
| Urban | 109394 (86.48) | 6.58 (6.54-6.62) | 20778 (84.69) | 1.29 (1.27-1.3) |
| Rural | 17108 (13.52) | 7.96 (7.83-8.08) | 3755 (15.31) | 1.63 (1.57-1.68) |
| Primary Tumour Site | ||||
| Scalp and neck | 19174 (14.9) | 1.03 (1.02-1.04) | 5904 (23.65) | 0.32 (0.31-0.33) |
| Limbs | 60035 (46.64) | 3.19 (3.16-3.22) | 10110 (40.5) | 0.55 (0.54-0.56) |
| Trunk | 49515 (38.47) | 2.62 (2.6-2.65) | 8950 (35.85) | 0.48 (0.47-0.49) |
| Stage | ||||
| Localised | 120779 (95.34) | 6.42 (6.38-6.46) | 22347 (90.84) | 1.21 (1.19-1.23) |
| Regional | 5368 (4.24) | 0.29 (0.28-0.29) | 1937 (7.87) | 0.1 (0.1-0.11) |
| Distant | 529 (0.42) | 0.03 (0.03-0.03) | 317 (1.29) | 0.02 (0.02-0.02) |
| Surgery | ||||
| Yes | 118659 (93.52) | 6.31 (6.27-6.35) | 23477 (95.47) | 1.27 (1.25-1.29) |
| No | 8226 (6.48) | 0.44 (0.43-0.44) | 1113 (4.53) | 0.06 (0.06-0.06) |
When examining primary tumour sites, SSMM lesions were predominantly located on the limbs (60,035, 46.64%), followed by the trunk (49,515, 38.47%) and scalp and neck (19,174, 14.9%). In terms of disease staging, the vast majority were localised cases (120,779, 95.34%), with only a small fraction presenting with distant metastasis (529, 0.42%). Surgical intervention was common, with 93.52% of patients (118,659) undergoing surgery.
During the study period, there were 24,520 recorded deaths. Among the deceased, 67.25% were male, 99.04% were white, and 60.71% were aged 70 or older. Mortality was notably higher among individuals from rural areas (15.31%) compared to their urban counterparts. Additionally, patients with a median household income below US$75,000 accounted for 55.57% of the total mortality, while SSMM located on the scalp, neck, and limbs showed higher mortality rates than other sites. Despite a high rate of localised cases and surgical treatments, mortality remained substantial within this population.
The trend of incidence rates
In this study, the trends in SSMM incidence rates from 2000 to 2021 were analysed using Joinpoint regression. Table 2 and Figure 1 provides an overview of the changing incidence rates across various demographic and clinical characteristics of SSMM. Overall, SSMM incidence rates exhibited a significant increase over this period, with an Average Annual Percent Change (AAPC) of 2.1% (95% CI: 1.7 to 2.5; p<0.001). Male patients and those aged 70 and older showed the most pronounced increase, particularly from 2012 to 2015.
| Table 2 Trends in SSMM incidence rates (2000-2021) | ||||||
|---|---|---|---|---|---|---|
Trends | ||||||
| Variables | AAPC (95% CI) | p-Value | Year | APC (95% CI) | p-Value | |
| Overall | 2.1* (1.7 to 2.5) | <0.001 | 2000-2012 | 0.9 (-0.2 to 1.6) | 0.082 | |
| 2012-2015 | 11.4* (5.8 to 14) | 0.003 | ||||
| 2015-2021 | 0.2 (-2.6 to 1.6) | 0.992 | ||||
| Sex | Male | 2.1* (1.6 to 2.5) | <0.001 | 2000-2012 | 1.1 (-0.1 to 1.8) | 0.06 |
| 2012-2015 | 11.2* (5.5 to 14) | 0.002 | ||||
| 2015-2021 | -0.1 (-3.1 to 1.3) | 0.732 | ||||
| Female | 2.1* (1.6 to 2.5) | <0.001 | 2000-2011 | 0.4 (-0.9 to 1.2) | 0.483 | |
| 2011-2015 | 9.0* (5.1 to 13.6) | 0.007 | ||||
| 2015-2021 | 0.9 (-2.8 to 2.5) | 0.507 | ||||
| Age at Diagnosis (y) | <60 | 0.5* (0 to -0.9) | 0.031 | 2000-2011 | -1.1 (-2.3 to -0.3) | 0.009 |
| 2011-2015 | 7.3 (3.7 to 11.6) | 0.004 | ||||
| 2015-2021 | -0.8 (-3.9 to 0.6) | 0.235 | ||||
| 60-69 | 3.0* (2.5 to 3.4) | <0.001 | 2000-2012 | 2.4 (0.9 to 3.1) | 0.024 | |
| 2012-2016 | 8.7 (4.9 to 13.1) | 0.006 | ||||
| 2016-2021 | 0.1 (-5.2 to 2.3) | 0.911 | ||||
| ≥70 | 4.4* (3.8 to 4.8) | <0.001 | 2000-2012 | 3.5 (2 to 4.3) | 0.004 | |
| 2012-2015 | 14 (7.6 to 17.1) | <0.001 | ||||
| 2015-2021 | 1.4 (-2.1 to 3.1) | 0.314 | ||||
| 2015-2021 | 1.4 (-2.1 to 3.1) | 0.314 | ||||
| 2011-2016 | 8.1* (5.3 to 13.4) | <0.001 | ||||
| 2016-2021 | -1.3 (-5.3 to 0.9) | 0.239 | ||||
| Black | -0.4 (-3.4 to 2.7) | 0.754 | 2000-2021 | -0.4 (-3.4 to 2.7) | 0.754 | |
| Asian | -0.3 (-0.3 to 1.5) | 0.756 | 2000-2021 | -0.3 (-1.9 to 1.5) | 0.756 | |
| Other | 2.4 (-0.1 to 5.1) | 0.064 | 2000-2021 | 2.4 (-0.1 to 5.1) | 0.064 | |
| Median Household Income | ≥75,000 | 0.8* (0.3 to 1.3) | 0.003 | 2000-2012 | -0.5 (-1.5 to 0.3) | 0.226 |
| 2012-2015 | 14.9* (7.9 to 18.3) | <0.001 | ||||
| 2012-2015 | 14.9* (7.9 to 18.3) | <0.001 | ||||
| <75,000 | 3.7* (3.1 to 4.4) | <0.001 | 2000-2011 | 2.4 (-2.3 to 3.5) | 0.134 | |
| 2011-2021 | 5.2* (4 to 11) | 0.006 | ||||
| Rural–Urban Distribution | Urban | 1.6* (1.1 to 2.0) | <0.001 | 2000-2011 | -0.1 (-1.3 to 0.8) | 0.78 |
| 2011-2015 ) | 9.1* (5.1 to 13.8 | 0.003 | ||||
| 2015-2021 | -0.1 (-3.3 to 1.5) | 0.781 | ||||
| Rural | 4.0* (3.6 to 4.5) | <0.001 | 2000-2021 | 4.0* (3.6 to 4.5) | <0.001 | |
| Primary Tumour | Site Scalp and neck | 2.1* (1.3 to 2.7) | <0.001 | 2000-2012 | 1.5 (-2 to 2.6) | 0.182 |
| 2012-2015 | 10.4* (3.7 to 14.2) | 0.016 | ||||
| 2015-2021 | -0.6 (-6.4 to 1.6) | 0.458 | ||||
| Limbs | 2.0* (1.5 to 2.3) | <0.001 | 2000-2012 | 0.8 (-0.3 to 1.5) | 0.126 | |
| 2012-2015 | 10.7* (5.3 to 13.3) | 0.004 | ||||
| 2015-2021 | 0.3 (-2.6 to 1.7) | 0.851 | ||||
| Trunk | 1.9* (1.4 to 2.3) | <0.001 | 2000-2011 | 0.1 (-1.2 to 1) | 0.931 | |
| 2011-2015 | 9.6* (5.5 to 14.5) | 0.003 | ||||
| 2015-2021 | 0.3 (-3 to 1.9) | 0.876 | ||||
| Stage | Localised | 1.6* (1.1 to 1.9) | <0.001 | 2000-2011 | -0.2 (-1.4 to 0.5) | 0.48 |
| 2011-2015 ) | 9.3* (5.7 to 13.9 | <0.001 | ||||
| 2015-2021 | 0 (-2.5 to 1.5) | 0.901 | ||||
| Regional | 2.9* (2 to 3.7) | <0.001 | 2000-2012 | 1.7 (-5.5 to 4.6) | 0.367 | |
| 2012-2021 | 4.6* (2.4 to 13.4) | 0.039 | ||||
| Distant | 1.3 (-2.1 to 4.6) | 0.364 | 2000-2015 | 7.8* (4.4 to 15.3) | <0.001 | |
| 2015-2021 | -13.3* (-37.8 to -2) | 0.02 | ||||
| Surgery | Yes | 1.4* (0.8 to 1.7) | <0.001 | 2000-2011 | 0.3 (-1.3 to 1.2) | 0.658 |
| 2011-2015 | 7.5* (3.6 to 11.8) | 0.006 | ||||
| 2015-2021 | -0.6 (-4.2 to 0.9) | 0.383 | ||||
| No | 10.1* (7.4 to13.7) | <0.001 | 2000-2006 | -3 (-31.4 to 9.3) | 0.595 | |
| 2006-2021 | 15.8* (12.3 to 32.7) | 0.01 | ||||
| APC: Annual Percent Change; AAPC: Average Annual Percent Change *Indicates that the AAPC is significantly different from zero at the alpha=0.05 level. | ||||||
 |
| Figure 1 Average annual trend of SSMM incidence. Age (A), sex and all (B), race (C), area distribution and income (D), site (E), stage and surgery (F). Each segment on the line represents the annual percent change (APC). |
The incidence trends in specific age groups varied significantly: individuals aged 60-69 years experienced an AAPC of 3.0% (95% CI: 2.5 to 3.4; p<0.001), while those 70 and older exhibited a notable rise with an AAPC of 4.4% (95% CI: 3.8 to 4.8; p<0.001). Additionally, incidence rates among patients of white ethnicity rose significantly, especially between 2011 and 2016 (APC=8.1%, 95% CI: 5.3 to 13.4; p=0.004)
The trends by tumour site indicated an increase for tumours located on the scalp and neck, with an APC of 10.4% (95% CI: 3.7 to 14.2; p<0.05) from 2012 to 2015, while tumours on the trunk showed a non-significant fluctuation across the periods. By stage, localised cases experienced a significant rise from 2011 to 2015, with an APC of 9.3% (95% CI: 5.3 to 13.9; p<0.001). Economic factors also played a role, as those with a median household income under US$75,000 demonstrated a significant increase in incidence rates (AAPC=3.7%, 95% CI: 3.1 to 4.4; p<0.001). Geographic location influenced trends as well, with rural areas exhibiting a higher AAPC of 4.0% (95% CI: 3.6 to 4.5; p<0.001).
Regarding surgical treatment, patients who underwent surgery saw an upward trend in incidence, particularly between 2011 and 2015 (APC=7.5%, 95% CI: 3.6 to 11.8; p=0.006), while those who did not undergo surgery showed a sharp increase earlier in the study period, especially from 2006 to 2021 (APC=15.8%, 95% CI: 12.3 to 32.7; p<0.05). This analysis provides a comprehensive understanding of SSMM incidence patterns over two decades, highlighting significant variations based on demographic and clinical factors.
The trend of incidence-based mortality rates
This analysis examines trends in SSMM incidence-based mortality rates from 2000 to 2021, revealing significant increases across various demographic and clinical categories (Table 3 and Figure 2). Overall, the mortality rate showed an AAPC of 19.9% (95% CI: 18.6 to 21.2; p<0.001). Male and female patients exhibited similar increasing trends, with females having a slightly higher AAPC of 21.4% (95% CI: 19.1 to 23; p<0.001).
| Table 3 Trends in SSMM-incidence-based mortality rates (2000-2021) | ||||||
|---|---|---|---|---|---|---|
Trends | ||||||
| Variables | AAPC (95% CI) | p-Value | Year | APC (95% CI) | p-Value | |
| Overall | 19.9* (18.6 to 21.2) | <0.001 | 2000-2002 | 145.1 (106.3 to 184.3) | <0.001 | |
| 2002-2005 | 32.0 (10.2 to 40.3) | <0.001 | ||||
| 2005-2021 | 7.7 (6 to 8.7) | 0.008 | ||||
| Sex | Male | 19.9* (18.6 to 21.2) | <0.001 | 2000-2002 | 163.8 (124.7 to 201.8) | <0.001 |
| 2002-2006 | 23.1 (13.3 to 34.1) | <0.001 | ||||
| 2006-2021 | 7.2 (5.3 to 8.3) | 0.006 | ||||
| Female | 21.4* (19.1 to 23) | <0.001 | 2000-2002 | 158.0 (95.5 to 211) | <0.001 | |
| 2002-2005 | 37.0 (4.4 to 47.4) | 0.026 | ||||
| 2005-2021 | 8.0 (3.4 to 10.4) | 0.028 | ||||
| Age at Diagnosis (y) | <60 | 19.1* (18.1 to 20.1) | <0.001 | 2000-2002 | 154.4 (123.8 to 188.2) | <0.001 |
| 2002-2005 | 31.5 (18.5 to 38.9) | <0.001 | ||||
| 2005-2021 | 6.3 (5.2 to 7.1) | 0.001 | ||||
| 60-69 | 19.8* (18.3 to 21.3) | <0.001 | 2000-2003 | 95.7 (71.4 to 135.3) | <0.001 | |
| 2003-2011 | 14.9 (11.5 to 24.9) | <0.001 | ||||
| 2011-2021 | 7.0 (0.1 to 9.2) | 0.049 | ||||
| ≥70 | 19.9* (18.4 to 21.2) | <0.001 | 2000-2002 | 158.0 (118 to 196) | <0.001 | |
| 2002-2006 | 24.2 (13.5 to 35.4) | <0.001 | ||||
| 2006-2021 | 7.2 (5.3 to 8.4) | 0.008 | ||||
| Race | White | 2.1* (19.4 to 22.4) | <0.001 | 2000-2002 | 161.5 (115 to 207.3) | <0.001 |
| 2002-2005 | 32.3 (9.1 to 41.4) | 0.001 | ||||
| 2005-2021 | 8.1 (5.8 to 9.4) | 0.011 | ||||
| Black | 6.2* (2.9 to 9.9) | <0.001 | 2000-2021 | 6.2 (2.9 to 9.9) | <0.001 | |
| Asian | 11.2* (5.3 to 17) | <0.001 | 2000-2004 | 51.3 (11.1 to 182.1) | 0.001 | |
| 2004-2021 | 3.5 (-11.4 to 7.8) | 0.332 | ||||
| Other | 19.5* (6.7 to 34.5) | <0.001 | 2000-2021 | 19.5 (6.7 to 34.5) | 0.003 | |
| Median Household Income | ≥75,000 | 23.2* (21.4 to 24.6) | <0.001 | 2000-2002 | 215.3 (165.2 to 263) | <0.001 |
| 2002-2007 | 21.3 (13.5 to 32.9) | <0.001 | ||||
| 2007-2021 | 8.4 (5.2 to 9.8) | 0.013 | ||||
| <75,000 | 18.5* (17.3 to 19.8) | <0.001 | 2000-2003 | 110.0 (87.1 to 128) | <0.001 | |
| 2003-2021 | 7.7 (6.7 to 8.8) | <0.001 | ||||
| Rural–Urban Distribution | Urban | 19.6* (18.3 to 20.8) | <0.001 | 2000-2002 | 145.4 (109.1 to 181.9) | <0.001 |
| 2002-2005 | 31.0 (10.1 to 39) | <0.001 | ||||
| 2005-2021 | 7.5 (5.9 to 8.5) | 0.006 | ||||
| Rural | 23.8* (21.4 to 25.6) | <0.001 | 2000-2002 | 218.9 (143.5 to 282.1) | <0.001 | |
| 2002-2008 | 22.5 (13.9 to 38) | <0.001 | ||||
| 2008-2021 | 7.6 (2.5 to 9.6) | 0.026 | ||||
| Primary Tumour Site | Scalp and neck | 16.8* (16.3 to 17.5) | <0.001 | 2000-2003 | 91.9 (83.6 to 101.5) | <0.001 |
| 2003-2008 | 14.1 (11.2 to 18.5) | <0.001 | ||||
| 2008-2021 | 5.2 (4.3 to 5.9) | <0.001 | ||||
| Limbs | 23.5* (21.2 to 25.5) | <0.001 | 2000-2002 | 262.7 (187 to 334.3) | <0.001 | |
| 2002-2009 | 15.7 (10.3 to 28.4) | 0.001 | ||||
| 2009-2021 | 7.2 (-3.2 to 9.5) | 0.079 | ||||
| Trunk | 19.7* (18.5 to 20.9) | <0.001 | 2000-2002 | 117.5 (82.5 to 150.5) | <0.001 | |
| 2002-2005 | 37.6 (11 to 45.7) | 0.002 | ||||
| 2005-2021 | 8.2 (6.9 to 9.2) | 0.007 | ||||
| Stage | Localised | 19.4* (18.1 to 20.5) | <0.001 | 2000-2002 | 148.3 (112.8 to 182.5) | <0.001 |
| 2002-2005 | 26.8 (10.8 to 33.8) | <0.001 | ||||
| 2005-2021 | 7.7 (6.2 to 8.7) | 0.005 | ||||
| Regional | 10.7* (6.5 to 15.3) | <0.001 | 2000-2021 | 10.7 (6.5 to 15.3) | <0.001 | |
| Distant | 5.1* (3 to 7.3) | <0.001 | 2000-2021 | 5.1 (3 to 7.3) | <0.001 | |
| Surgery | Yes | 20.6* (19.2 to 22) | <0.001 | 2000-2002 | 175.0 (132.1 to 217.8) | <0.001 |
| 2002-2006 | 25.0 (14.5 to 37.1) | <0.001 | ||||
| 2006-2021 | 7.1 (5.3 to 8.2) | 0.004 | ||||
| No | 14.5* (13 to 16.2) | <0.001 | 2000-2021 | 14.5 (13 to 16.2) | <0.001 | |
APC: Annual Percent Change; AAPC: Average Annual Percent Change. *Indicates that the AAPC is significantly different from zero at the alpha=0.05 level. | ||||||
 |
| Figure 2 Average annual trend of SSMM incidence-based mortality. Age (A), sex and all (B), race (C), area distribution and income (D), site (E), stage and surgery (F). Each segment on the line represents the annual percent change (APC). |
Patients aged 60-69 displaying an AAPC of 19.8% (95% CI: 18.3 to 21.3; p<0.001), while those aged 70 and above experienced similar growth (AAPC=19.9%, 95% CI: 18.4 to 21.2; p<0.001). Race-specific trends highlight that White patients had a pronounced increase in mortality (AAPC=21.0%, 95% CI: 19.4 to 22.4; p<0.001), while Black and Asian patients saw smaller but statistically significant increases.
The impact of socioeconomic status is evident, as patients with household incomes below $75,000 had a mortality AAPC of 18.5% (95% CI: 17.3 to 19.8; p<0.001), slightly lower than those with incomes above $75,000 (AAPC=23.2%, 95% CI: 21.4 to 24.6; p<0.001). Geographically, rural patients experienced a slightly higher increase (AAPC=23.8%, 95% CI: 21.4 to 25.6; p<0.001) compared to urban residents.
By primary tumour site, mortality trends were highest for lesions on the limbs (AAPC=23.5%, 95% CI: 21.2 to 25.5; p<0.001), followed by those on the trunk and scalp/neck. In terms of disease staging, localised cases experienced substantial increases (AAPC=19.4%, 95% CI: 18.1 to 20.5; p<0.001). Mortality trends for patients undergoing surgery reflected a marked rise (AAPC=20.6%, 95% CI: 19.2 to 22; p<0.001), emphasizing the elevated risks even among treated cases.
Overall, these findings underscore significant rises in mortality associated with SSMM, with notable variations influenced by demographic factors, tumour location, and treatment status.
Discussion
Our study offers a comprehensive examination of SSMM incidence and mortality trends over a two-decade period using data from the SEER database, which covers a significant portion of the U.S. population. For the first time, this analysis employed Joinpoint regression to assess SSMM incidence and mortality across various demographics and clinical characteristics, providing a nuanced view of how these trends have evolved.
SSMM represents one of the most common and aggressive forms of cutaneous melanoma, accounting for approximately 70% of melanoma cases. It predominantly affects individuals with fair skin and typically exhibits two distinct growth phases: an initial radial growth phase within the epidermis and dermis, characterised by slow progression, followed by an aggressive vertical growth phase.12,20,21 While SSMM generally has a better survival rate than nodular melanoma or acral lentiginous melanoma, the BRAF mutation rate in SSMM can reach up to 66%. Once such mutations occur or the lesion progresses to invasive growth, the prognosis for SSMM significantly worsens.22-24
Our findings underscore the significant increase in both incidence and incidence-based mortality of SSMM. The age-adjusted incidence rate during the study period reached 6.98 per 100,000 (95% CI: 6.94-7.01), exhibiting a generally upward trend with an AAPC of 2.1%. Notably, the rate of increase was most pronounced between 2012 and 2015, during which the APC soared to 11.4%. The incidence-based mortality rate from 2000 to 2021 was recorded at 1.33 per 100,000 (95% CI: 1.31-1.34), with an AAPC of 19.9%. This mortality rate experienced a sharp rise from 2000 to 2002, with an APC of 145.1% (95% CI: 106.3-184.3), followed by a more gradual increase thereafter. These trends suggest that SSMM represents an increasingly severe public health issue. Notably, the rise in incidence was particularly evident among older individuals, with rates reaching 23.36 per 100,000 (95% CI: 23.12-23.60), and among White patients, with rates of 8.36 per 100,000 (95% CI: 8.32-8.41). Among those over 60 years of age, the incidence consistently increased, while for White individuals, there was a rapid rise in incidence from 2011 to 2016 (APC: 8.1%, 95% CI: 5.3-13.4), followed by a slow decline after 2016 (APC: -1.3%, 95% CI: -5.3-0.9). Previous studies have suggested that the higher incidence among White individuals may be attributable to increased susceptibility to UV-induced skin damage, which aligns with our findings that SSMM is more prevalent in sun-exposed areas such as the head, face, and neck regions.25,26
A closer examination of the mortality trends reveals that the most significant increase occurred in older age groups, particularly those over 70, with an AAPC of 19.9% (95% CI: 18.4-21.2). However, the rate of increase slowed post-2011. Higher mortality rates among older patients may be attributed to a greater prevalence of comorbidities.5,27 Furthermore, the advent of targeted therapies and immunotherapies has contributed to a reduction in mortality. Our results indicate that mortality among White individuals has also risen consistently, with a notable acceleration between 2000 and 2005. This trend may be partially explained by the historically higher incidence rates among White populations. Additionally, as Whites comprise the majority of cases in the database, there is potential for bias concerning other racial groups.28,29
The incidence of SSMM shows no significant gender differences; however, mortality rates are notably higher in males at 2.24 per 100,000 (95% CI: 2.21-2.28), compared to females at 0.73 per 100,000 (95% CI: 0.72-0.75). Both incidence and mortality rates for males and females exhibit a general upward trend, though mortality rates began to decelerate around 2006.30,31 Socioeconomic factors have also played a critical role. Over the past two decades, overall incidence and mortality rates remained comparable across patients of varying household incomes and residential areas, showing no substantial differences. However, post-2011, changes in the rate of incidence growth were observed, with greater fluctuations in low-income (3.7 per 100,000, 95% CI: 3.1-4.4) and rural populations (4.0 per 100,000, 95% CI: 3.6-4.5) in terms of AAPC. Similarly, with respect to mortality, high-income and urban patients showed a marked deceleration in growth around 2011. These findings indicate that disparities in access to healthcare, early diagnosis, and treatment options likely contribute to these outcomes.32-34 This underscores the need for healthcare policy reforms aimed at enhancing access to SSMM care in underserved communities. Interestingly, despite advancements in treatment, overall mortality continues to rise, likely reflecting the impact of SSMM metastasis, as there remains no curative option for metastatic SSMM at present.
Moreover, our analysis of tumour location indicates that the incidence rate for the extremities, at 3.19 per 100,000 (95% CI: 3.16-3.22), surpasses that of the head and neck (1.03 per 100,000, 95% CI: 1.02-1.04) and the trunk (2.62 per 100,000, 95% CI: 2.60-2.65), suggesting that SSMM is more prevalent in sun-exposed areas, consistent with previous reports. However, there were no significant differences in the overall mortality rates of SSMM based on tumour location-head and neck, extremities, or trunk-indicating that once SSMM is diagnosed, tumour location does not substantially affect mortality.35-37 An intriguing phenomenon is the rapid increase in incidence observed from 2012 to 2015. This trend may be attributable to heightened diagnostic vigilance for SSMM following the introduction of immunosuppressive therapies. Across all tumour locations, mortality rates have exhibited a gradual decline over the years.
Notably, the majority of SSMM cases are at the stage of localised infiltration, with an incidence rate of 6.42 per 100,000 (95% CI: 6.38-6.46), and a high proportion of patients, 93.52%, opt for surgical intervention. Regarding mortality, our findings reveal that the growth rate of mortality for patients with localised infiltration began to decline post-2005, reaching 7.7 per 100,000 (95% CI: 6.2-8.7). In contrast, mortality rates among those with regional metastasis, at 10.7 per 100,000 (95% CI: 6.5-15.3), and distant metastasis, at 5.1 per 100,000 (95% CI: 3.0-7.3), have remained on a steep upward trajectory. Correspondingly, for patients undergoing surgical intervention, the mortality growth rate decreased to 7.1 per 100,000 (95% CI: 5.3-8.2) after 2006, whereas those without surgical intervention experienced a persistent increase in mortality, reaching 14.5 per 100,000 (95% CI: 13.0-16.2). These findings suggest a decline in mortality trends as treatment options have expanded to include radiotherapy, chemotherapy, targeted therapy, and immune checkpoint inhibition.38-41 This indicates that a multidisciplinary approach for early-stage SSMM may improve survival outcomes, while for advanced SSMM, survival may be prolonged, though mortality remains comparatively high.
The consistency in mortality trends across regions, regardless of income levels, suggests that individual clinical factors and the availability of timely interventions exert a greater influence than socioeconomic status alone. However, the disparities in incidence and mortality rates among different population groups underscore the importance of tailored strategies for prevention, early detection, and treatment.
In conclusion, the overall incidence and mortality rates of SSMM continue to rise, underscoring the urgent need for strengthened public health efforts, particularly in education around sun protection, early screening, and equitable access to care. The noticeable slowdown in mortality growth around 2005 suggests that changes in treatment modalities have had a positive impact on mortality rates. Looking ahead, future research should focus on the development of targeted therapies and investigate whether various demographic characteristics may serve as independent prognostic factors for SSMM. This study lays the groundwork for further investigation into the underlying factors driving these trends and emphasizes the importance of a robust, multifaceted approach to alleviating the burden of SSMM.
Limitations
This study has several limitations. As a retrospective descriptive analysis, it is susceptible to selection bias. Moreover, due to the lack of comparable studies, our findings cannot be directly contrasted with SSMM incidence and mortality trends in other regions or countries. The SEER database is predominantly representative of White populations, limiting our ability to fully assess racial disparities across diverse groups. Additionally, the absence of data on systemic therapy in the SEER database restricts our capacity to evaluate the impact of various treatments on mortality outcomes in SSMM patients. Future research should address these limitations by incorporating more diverse populations and treatment data.
Conclusions
From 2000 to 2021, SSMM incidence rose with an AAPC of 2.1%, particularly from 2000 to 2012, while mortality saw a substantial increase before stabilising somewhat. These trends were predominantly influenced by individual factors like age, sex, race, tumour site, and stage, whereas socioeconomic status and regional differences had minimal impact. This analysis underscores the importance of demographic-specific interventions and could inform future public health strategies. However, further research is needed to validate these factors as definitive risks and to monitor trends beyond 2021.
Acknowledgement
This study does not involve any personal, financial, or other conflicts of interest.
Authors' contributions
All authors had full access to all of the data in the study. Doc. Zhaohan Liu and Liehua Deng take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Hai Yu. Acquisition, analysis, or interpretation of data: Zhaohan Liu, Hai Yu and Jinrong Zhang. Drafting of the manuscript: Zhaohan Liu and Hai Yu. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Zhaohan Liu , Hai Yu and Jinrong Zhang. Administrative, technical, or material support: Wai Chi Lau and Jun Lyu. Supervision: Jun Lyu and Liehua Deng. All authors contributed to writing of the manuscript and approved the final version.
Conflicts of interest
The authors declare no conflict of interest. The funders had no role in the design of the study.
Ethics approval
The NCI SEER study is retrospective in nature, and the ethics committee waived consent due to the study's anonymised data and guarantee of patient privacy.
Data availability statement
Publicly available datasets were analysed in this study. This data can be found at: https://seer.cancer.gov.
Acknowledgments
We thank all SEER database staff and scientists.
Funding
This research was funded by Key Scientific Problems and Medical Technical Problems Research Project of China Medical Education Association (grant number 2022KTZ009, 2024KTZ014) and Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization (grant number 2021B1212040007).
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