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Original Article
ARTICLE IN PRESS
doi:
10.25259/IJDVL_352_2022

Survival rates for invasive cutaneous malignant melanoma in South Korea in accordance with the Eighth edition AJCC Cancer Staging Manual: A retrospective single center study

Department of Dermatology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
Department of Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea
Corresponding author: Prof. Jun Young Kim and Prof. Seok-Jong Lee, Department of Dermatology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, South Korea. 198kjy@hanmail.net
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Lee SH, Ha GU, Lee HJ, Chung HY, Huh S, Ha D-L et al. Survival rates for invasive cutaneous malignant melanoma in South Korea in accordance with the Eighth edition AJCC Cancer Staging Manual: A retrospective single center study. Indian J Dermatol Venereol Leprol doi: 10.25259/IJDVL_352_2022

Abstract

Background

Cutaneous malignant melanoma is known to have a poorer prognosis in Asian patients as compared to Caucasians. Few studies have analysed the overall survival rate (OS) and melanoma-specific survival rate (MSS) of patients with cutaneous malignant melanoma in South Korea.

Aim

This study aims to analyse the OS, MSS and prognostic factors of patients with invasive cutaneous malignant melanoma in South Korea.

Methods

The medical records of patients diagnosed with invasive cutaneous malignant melanoma from July 2006 to June 2016 at Kyungpook National University Hospital were reviewed retrospectively. The OS/MSS of these patients were calculated in accordance with the Eighth American Joint Committee on Center staging system and the prognostic factors affecting MSS were analysed.

Results

A total of 202 patients with a mean age of 61.5 years were included. The 5-year OS/MSS was 64.4%/70.7% in the patients. The 5-year OS/MSS was 94.7%/97.1% for stage I, 67.2%/76.3% for stage II, 54.4%/59.1% for stage III, and 0%/0% for stage IV. On univariate analysis, the age, sex, Breslow thickness, ulceration, microsatellites, satellites, locally recurrent or in-transit metastasis, tumour metastasis in sentinel lymph nodes and clinicopathological stage were all significantly associated with the MSS, but not with acral distribution or BRAF mutation status. However, on multivariate analysis only the Breslow thickness, ulceration and stage IV were significantly associated with the MSS.

Limitations

This study was conducted retrospectively in a relatively small number of patients at a single tertiary center in South Korea.

Conclusions

The OS/MSS of patients with invasive cutaneous malignant melanoma in South Korea was lower than those in Caucasians. In addition to the Breslow thickness and ulceration, the impact of tumour location and sentinel nodal metastasis on cutaneous malignant melanoma should be reevaluated to better understand the disease prognosis in these patients.

Keywords

Epidemiology
Korea
malignant melanoma
prognostic factors
survival rate

Plain Language Summary

This study investigates the survival of patients with invasive cutaneous malignant melanoma (a type of skin cancer) in South Korea. A review of the medical records of 202 patients with melanoma found that the survival rate was lower in South Korea compared to Caucasians. Factors influencing survival included the thickness of the cancer, the presence of ulceration and the stage of the melanoma. The authors suggest that more attention should be given to the depth of the cancer invasion and its condition (whether it had ulcerated or not), rather than where the cancer is located and whether it has spread to lymph nodes to better understand the prognosis of invasive cutaneous malignant melanoma in South Korea. However, this study only looked at a small number of patients in one hospital, so more research is needed.

Introduction

Cutaneous malignant melanoma is an uncommon, but lethal, form of skin cancer. Its incidence is steadily rising, resulting in a significant increase in disease burden. The age-standardized worldwide incidence rate of cutaneous malignant melanoma increased 13% between 2012 and 2020 (from 3.0 to 3.4/100,000/year). 1,2 In South Korea the incidence increased from 2.6 to 3.0/100,000/year between 2004 and 2017. 3

Asian patients with cutaneous malignant melanoma typically exhibit a more prominent acral distribution, advanced disease at diagnosis, and poorer prognosis compared to Caucasians. 4 The poorer prognosis has been noted even in Asian–American patients living in the USA: among 49,772 patients with invasive cutaneous malignant melanoma in the US reported by Cormier et al., the 5-year overall survival rate (OS) was 80.2% in Asian-American patients compared to 89.6% in Caucasian patients. 5 This suggests that ethnic and genetic factors may be more important than environmental factors (geographical location, ultraviolet radiation exposure) in influencing the prognosis of cutaneous malignant melanoma. 4,5

The American Cancer Society reported melanoma-specific survival rates (MSS) in accordance with the staging criteria of the 8th edition of the American Joint Committee on Center (AJCC) staging system in 2017. Among 43,792 patients from 10 institutions in the USA, Europe, and Australia from 1998, the 5-year MSS in patients with stages I, II and III of the diseases were 98%, 90%, and 77%, respectively. 6 However, a recent retrospective study in patients with melanoma from South Korea using a customized research database from the National Health Insurance Sharing Service in 2002–2017 reported a much lower 5- and 10-year OS of 62.3 and 48.8%, respectively . 7

Although an accurate understanding of survival rates is important for patient counseling, only a few studies have analysed the OS and MSS of cutaneous malignant melanoma patients in South Korea. Thus, we aimed to analyse the OS, the MSS, and prognostic factors in patients with invasive cutaneous malignant melanoma in South Korea.

Methods

This study was conducted at Kyungpook National University Hospital, a tertiary centre in South Korea and was approved by the institutional review board (KNUH 2021-07-024). Medical records from the hospital database between July 2006 and June 2016 were retrospectively reviewed and a total of 301 patients histologically diagnosed with malignant melanoma were retrieved.

The study only included patients diagnosed with primary invasive cutaneous malignant melanoma. Patients whose medical records were insufficient for clinical or pathological staging, those with a histological diagnosis of cutaneous malignant melanoma in situ or atypical melanocytic proliferation and those who presented with mucosal malignant melanoma or metastatic melanoma with unknown primary were excluded.

Thus, only 202 patients with invasive cutaneous malignant melanoma were included in the final analysis. The stages of all invasive cutaneous malignant melanomas were revised according to the 8th edition of the AJCC staging system.

The following data were collected:

  1. Clinical characteristics: age at diagnosis, gender, duration from disease onset to the first visit, and anatomic location

  2. Histopathological characteristics: including Breslow thickness, ulceration, presence of microsatellites, satellites, locally recurrent or in-transit metastasis, presence of tumour in sentinel lymph node, BRAF mutation status and clinicopathological stage

  3. Follow-up data: date of mortality, OS, MSS, and follow-up period

The date of mortality was identified by checking the date of expiration from the National Health Insurance Sharing Service. Although other potential prognostic factors, such as family or personal history of melanoma were noted, they were not included in this study owing to their rarity among the patient population. The data were analysed and 3- and 5-year OS/MSS were calculated.

The Kaplan–Meier method was used to draw survival curves to estimate the OS and MSS of invasive cutaneous malignant melanoma patients. The difference between survival curves was determined by a log-rank test calculating the corresponding p values. The Cox proportional hazard model was used for both univariate and multivariate analyses to estimate prognostic factors associated with MSS. The statistically significant factors in the univariate analysis were consecutively tested using multivariate analysis. All statistical analyses were performed using PASW Statistics 18 (Release Version 18.0.0, SPSS, Inc., 2009, Chicago, IL, www.spss.com) and P < 0.05 was considered significant.

Results

Clinicopathological characteristics

The clinicopathological details of the 202 patients in this study are summarised in Table 1. There were 104 males and 98 females and the male to female ratio was 1:0.94. The mean age was 61.5 years and the majority of patients (149; 73.8%) were aged between 51 and 80 years. The duration of the disease at presentation showed bimodal peaks at <1 year (47; 24.2%) and >10 years (50; 25.8%).

Table 1:: Clinicopathological characteristics of 202 patients with invasive cutaneous malignant melanoma
202 invasive cutaneous malignant melanomas (%)*
Follow-up (months) 69.7 ± 41.7
Sex (male:female) 104:98
Age 61.5 ± 13.6
Age ≤30 3 (1.5)
31–40 13 (6.4)
41–50 26 (12.9)
51–60 47 (23.3)
61–70 59 (29.2)
71–80 43 (21.3)
>80 11 (5.4)
Duration from disease onset to the first visit (years)
n < 1 47 (24.2)
1≤ n <2 28 (14.4)
2≤ n <3 22 (11.3)
3≤ n <5 30 (15.5)
5≤ n <10 17 (8.8)
n > 10 50 (25.8)
N/A a 8
Primary sites
Head and neck 31 (15.3)
Upper extremities 9 (4.5)
Hands 26 (12.9)
Fingernail 14 (6.9)
Others 12 (5.9)
Lower extremities 11 (5.4)
Feet 100 (49.5)
Toenail 16 (7.9)
Others 84 (41.6)
Trunk 25 (12.4)
Breslow thickness (mm)
<0.8 12 (6.0)
0.8-1 19 (9.5)
1.01–2 32 (16.0)
2.01–4 43 (21.5)
>4 94 (47.0)
N/A a 2
Ulceration
Positive 122 (60.7)
Negative 79 (39.3)
N/A a 1
MSI
Positive 29 (14.4)
Negative 172 (85.6)
N/A a 1
Presence of tumour in sentinel lymph node
Positive 34 (26.0)
Negative 97 (74.0)
N/A a 71
BRAF mutation
Positive 11 (11.7)
Negative 83 (88.3)
N/A a 108
Clinicopathological subtype
ALM 125 (64.4)
Non-SUM 95 (49.0)
SUM 30 (15.5)
SSM 41 (21.1)
NM 21 (10.8)
LMM 7 (3.6)
N/A a 8
Values are presented as mean ± standard deviation or number (%).

MSI: microsatellites, satellites, locally recurrent, and in-transit metastasis; ALM: acral lentiginous melanoma; SUM: subungual melanoma; SSM: superficial spreading melanoma; NM: nodular melanoma; LMM: lentigo maligna melanoma.

N/A: not available, excluded in the calculation of percentages.

The melanomas were located on the hands and feet in 126 (62.4%) patients, with the feet alone accounting for 100 patients (49%). The most common clinicopathological subtype was acral lentiginous melanoma (125; 64.4%) and this included subungual melanomas (30; 15.5%) [Table 1]. A Breslow thickness of >4 mm was seen in 94 (47.0%) patients and visible or microscopical ulceration was noted in 122 (60.7%) patients at presentation. Microsatellites, satellites, locally recurrent or in-transit metastasis were observed in 29 (14.4%) patients. Sentinel lymph node biopsies were performed in 131 (64.9%) patients and sentinel node involvement was noted in 34 (26.0%) patients. Only 11 (11.7%) of the 94 (46.5%) patients in whom BRAF mutation analysis was performed had mutations. The average follow-up period was 69.7 months.

Overall survival and melanoma-specific survival

The OS/MSS of patients in this study are summarized in Table 2. The 3- and 5-year OS/MSS were 72.3%/77.6% and 64.4%/70.7%, respectively. Of the patients, 40 (19.8%), 84 (41.6%), 66 (32.7%) and 12 (5.9%) were categorized as stages I, II, III and IV, respectively. For stages I–IV, the 5-year OS was 94.7%, 67.2%, 54.4% and 0.0% and the 5-year MSS was 97.1%, 76.3%, 59.1% and 0.0%, respectively [Table 2]. The median survival time for stages II, III and IV were estimated as 10.42 (7.62–13.21 years), 5.42 (2.75–8.09 years) and 0.83 (0.27–1.40 years) years, respectively. The median survival time for stage I could not be estimated because of the small number of mortalities. The OS and MSS according to substages following the 8th edition of the AJCC staging system are shown in Table 2. A considerable decrease in the 5-year MSS was observed between stages IIA (88.5%) and IIB (74.3%) [Table 2].

Table 2:: The 3- and 5-year survival rates of 202 patients with invasive cutaneous malignant melanoma in South Korea for stages following the 8th edition of AJCC staging system
Stage N Overall survival
Melanoma-specific survival
3 years (%) 5 years (%) 3 years (%) 5 years (%)
Total - 202 72.3 64.4 77.6 70.7
8th AJCC Stages I–IV I 40 97.5 94.7 100 97.1
II 84 76.2 67.2 83.8 76.3
III 66 63.6 54.4 67.3 59.1
IV 12 8.3 0.0 11.1 0.0
8th AJCC Substages IA–IV IA 22 95.5 95.5 100 100
IB 18 100 92.9 100 92.9
IIA 18 83.3 83.3 88.5 88.5
IIB 35 77.1 64.9 85.0 74.3
IIC 31 71.0 60.4 79.5 70.9
IIIA 3 66.7 66.7 - a - a
IIIB 11 100 90.9 100 90.9
IIIC 36 66.7 57.8 70.8 64.4
IIID 16 31.3 18.8 31.3 18.8
IV 12 8.3 0.0 11.1 0.0

AJCC: American Joint Committee on Center; N: number of patients.

Not calculated because all cases are censored.

Prognostic factors associated with melanoma survival

Potential MSS prognostic factors in patients identified by univariate analyses were age at diagnosis, sex, Breslow thickness, ulceration, microsatellites, satellites, locally recurrent, and in-transit metastasis, presence of tumour in sentinel lymph node and clinicopathological stage but not acral distribution or BRAF mutation status. [Table 3].

However, on multivariate analysis only Breslow thickness, ulceration, the clinicopathological stages were found to be statistically significant independent prognostic factors [Table 4]. Stages IV was found to be independent prognostic factors but on grouping the substages, the MSS between stages I–IIA and IIB–IV were not statistically significant despite the abrupt drop in survival rate from stage IIB.

Table 3:: Univariate analyses of prognostic factors for melanoma-specific survival rates in patients with invasive cutaneous malignant melanoma
Score Degree of freedom p value Exp(B)
Age at diagnosis 4.603 1 0.032*
Sex 4.615 1 0.032*
Duration from disease onset to the first visit 0.079 1 0.779
Primary sites 7.474 5 0.188
Acral/nonacral area 0.655 1 0.418
Clinicopathological subtype 1.161 3 0.762
Breslow thickness 37.819 1 <0.001*
Ulceration 24.131 1 <0.001*
MSI 4.786 1 0.029*
Presence of tumour in sentinel lymph node 17.182 1 <0.001*
BRAF mutation 0.107 1 0.743
Clinicopathological stage 105.806 3 <0.001*
Stage II 1.068 1 0.051 2.909
Stage III 1.904 1 <0.001* 6.714
Stage IV 3.882 1 <0.001* 48.520
p < 0.05, statistically significant.

Exp(B): exponentiated coefficient; MSI: microsatellites, satellites, locally recurrent, and in-transit metastasis.

Table 4:: Multivariate analyses of prognostic factors for melanoma-specific survival rates in patients with invasive cutaneous malignant melanoma
B SD p value Exp(B)
Breslow thickness 0.082 0.042 0.050* 1.086
Ulceration 1.082 0.535 0.043* 2.950
Clinicopathological stage 0.001*
Stage II 0.189 0.841 0.823 1.208
Stage III 1.267 1.066 0.235 3.549
Stage IV 4.754 1.408 0.001* 116.103
p < 0.05, statistically significant.

B: regression coefficient; SD: standard deviation; Exp(B): exponentiated coefficient.

Discussion

Studies have shown that Asians with cutaneous malignant melanoma have a poorer prognosis as compared with Caucasians . 4,6,813 In 2017, the American Cancer Society reported the 5-year MSS for stages I-III based on the 8th edition of the AJCC staging system. The survival rates were 99% for stage IA, 97% for stage IB, 94% for stage IIA, 87% for stage IIB, 82% for stage IIC, 93% for stage IIIA, 83% for stage IIIB, 69% for stage IIIC, and 32% for stage IIID [Table 5]. 6 According to the Cancer Statistics 2020 report, the 5-year relative survival rate for cutaneous malignant melanoma with distant metastasis (stage IV) was 25%. 8 Previous reports on survival rates of cutaneous malignant melanoma patients in Asian countries such as Japan, China, Singapore, and Taiwan have consistently shown lower rates compared to those in Western countries [Table 5]. 6,913 Our study confirms the poorer prognosis of Asian patients with cutaneous malignant melanoma.

Table 5:: Summary of recent survival analyses for cutaneous malignant melanoma patients in Western and Asian countries following the staging criteria of the American Joint Committee on Center
Patients’ ethnicity Study period Edition of AJCC stages Stage N Overall survival Stage N Melanoma-specific survival
5-year (%) 5-year (%)
AJCC (2017) USA, Europe, Australia Beginning 1998 8th IA 5,225 99
IB 5,749 97
IIA 2,338 94
IIB 1,688 87
IIC 691 82
IIIA 1,006 93
IIIB 1,170 83
IIIC 2,201 69
IIID 205 32
JSCS (2019) Japan 2005–2017 7th IA 483 98.0
IB 316 93.9
IIA 238 94.8
IIB 260 82.4
IIC 182 71.8
IIIA 181 75
IIIB 309 61.3
IIIC 278 41.7
IV 198 17.7
Yeo et al. (2021) Singapore 1996-2015 7th I 19 100
II 25 45.7
III 15 43.1
IV 1
Zhang et al. (2017) China 2001-2010 7th I 8 37.5
II 31 32.3
III 44 0.0
IV 15 0.0
Chi et al. (2011) China 2006–2010 6th I 32 94.1
II 292 44.0
III 131 38.4
IV 67 4.6
Chang et al. (2004) Taiwan 1992–2001 5th I 47 84.4
II 23 56.0
III 58 34.7
IV 43 0.0
This study (2021) Korea 2006–2016 8th I 40 94.7 IA 22 100
IB 18 92.9
II 84 67.2 IIA 18 88.5
IIB 35 74.3
IIC 31 70.9
III 66 54.4 IIIA 3
IIIB 11 90.9
IIIC 36 64.4
IIID 16 18.8
IV 12 0.0 IV 12 0.0

AJCC: American Joint Committee on Center; JSCS: Japanese Skin Cancer Society; N: number of patients.

Although both the Western report 6 and our current study showed a decrease in 5-year MSS between stages IIA and IIB, from 94 to 87% and from 88.5 to 74.3%, the decrease (7% vs 14.2%) is much greater in our study [Table 5]. We feel that adjuvant cancer therapy should also be administered in in Korean patients with stages IIB and IIC. Also, and careful monitoring of the prognosis of stages IIB and IIC patients is necessary.

Earlier studies have associated tumour thickness, ulceration and advanced stage as factors contributing to the poor prognosis in Asian cutaneous malignant melanoma patients. 6,14 and our study confirms these as independent prognostic factors.

The reasons why Asian patients tend to present with more advanced stages of the disease are a matter of controversy. Some reports emphasized the predominant acral distribution as a major difference in ethnicities and suggested that the acral melanoma itself carries a worse prognosis due to its natural aggressive histopathologic features. 15,16 However, a Japanese study reported no survival difference between acral and non-acral melanoma patients, 17 and a recent Korean study noted a better prognosis in patients with acral melanoma than non-acral melanoma located on the trunk. 18 The acral location was not a prognostic factor in our study and acral melanomas may have a similar prognosis to malignant melanomas at other cutaneous sites if properly treated.

The sentinel lymph node biopsy is a widely accepted diagnostic procedure to determine nodal staging for cutaneous malignant melanoma patients and presence of tumour in sentinel lymph nodes is one of the important predictors of relapse-free survival and OS. 19 However, several recent reports have demonstrated that the presence of tumour in sentinel lymph nodes is not an independent predictive factor of relapse or survival, 20 and this was confirmed in our study too.

BRAF and NRAS mutations are anticancer targets in melanoma and may have prognostic value. BRAF and NRAS mutations are present in 80% of all sporadic melanomas in Caucasians. However, BRAF mutations were present in only 30.4%–41.8% in Japan, 25.5% in China, 14.3% in Taiwan, respectively and in 11.9–19.4% in Korea, and NRAS mutations were present in 12.3% in Japan, 7.2% in China, 10.1% in Taiwan and 12.6%in Korea. 4,18,21 Similarly in our study, the frequency of BRAF mutation was 11.7%. The lower frequency of BRAF and NRAS mutation in Asian patients with cutaneous malignant melanoma may result in a lower utility of immune checkpoint inhibitors (ICIs; vemurafenib, dabrafenib, or trametinib). 4,18

Mutations in BRAF genes did not influence the prognosis in our study and conflicting results have been reported in previous studies. 22 Further studies with large number of patients will be needed to determine whether the BRAF mutation status, with or without ICI and BRAF/MEK inhibitor therapy, plays a significant role in prognosis of invasive cutaneous malignant melanoma.

In addition, the difference in the timing of the introduction of ICIs by each country could also be the other contributing prognostic factor. ICIs had started to gain approval from the Food and Drug Administration for metastatic melanoma treatment beginning 2011, 23 but the aforementioned survival studies in China and Taiwan were conducted before 2011. In Japan, the Ministry of Health, Labour and Welfare has approved coverage for ICIs beginning 2014, 24 and ICIs had gained approval from the Ministry of Food and Drug Safety in Korea beginning 2014 and have been subject to insurance benefits from 2017. 7 In this study, most of the stage IV patients did not receive ICI treatment, and the 5-year OS/MSS of stage IV was low like 0%/0% and this could be a factor responsible for the lower survival rate [Table 5].

Our study has several limitations. As it was a retrospective analysis conducted at a single institution in South Korea and involved a relatively small number of patients, it was not possible to estimate survival rates for patients with stage IIIA melanoma. Furthermore, the study only compared melanoma survival rates reported by different countries and failed to take into consideration crucial factors such as governmental insurance support and timing of the study, which could potentially influence the results. Lastly, the study identified a perplexing paradox where the MSS for stage IIIB was higher than that of stage II, and a similar pattern was observed in data from the American Cancer Society for IIC and IIIA in 2017 [Table 5]. The reason behind this survival paradox is not apparent and requires further investigation through future studies to determine a more realistic survival rate according to the AJCC staging system.

Conclusion

This study presents 5-year OS and MSS as reference values for estimating survival rates of invasive cutaneous malignant melanoma patients in South Korea and showed that the prognosis was worse than that of Caucasians. In addition to already well-verified Breslow thickness and ulceration, the impact of tumour location and sentinel nodal metastasis on MSS should be reconsidered to better understand the prognosis of invasive cutaneous malignant melanoma patients in South Korea.

Declaration of patient consent

Institutional Review Board (IRB) permission obtained for the study.

Financial support and sponsorship

Nil.

Conflict of interest

There are no conflict of interest.

References

  1. International Agency for Research on Cancer. Global Cancer Observatory. Globocan 2020. Melanoma of skin. Available from: https://gco.iarc.fr/today/fact-sheets-cancers.
  2. , , , et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:e359-86.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , , et al. Incidence and survival rates of cutaneous melanoma in South Korea using national health insurance claims data. Cancer Res Treat 2021 Sep 30 doi: 10.4143/crt.2021.871. Epub ahead of print
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  4. , , , et al. Sunrise in melanoma management: time to focus on melanoma burden in Asia. Asia-Pac J Clin Oncol. 2017;13:423-7.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , et al. Ethnic differences among patients with cutaneous melanoma. Arch Intern Med. 2006;166:1907-14.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67:472-92.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  7. , , , . Survival and economic burden of melanoma: a retrospective cohort analysis in South Korea. Yakhak Hoeji. 2020;64:257-64.
    [Google Scholar]
  8. , , . Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7-30.
    [CrossRef] [PubMed] [Google Scholar]
  9. , , , et al. Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma. Cancer Medicine. 2019;8:2146-56.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  10. , , , et al. Melanoma in Singapore: a 20-year review of disease and treatment outcomes. Ann Acad Med Singap. 2021;50:456-66.
    [CrossRef] [PubMed] [Google Scholar]
  11. , . Clinical and prognostic factors in 98 patients with malignant melanoma in China. J Int Med Res. 2017;45:1369-77.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  12. , , , et al. Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: a study of 522 consecutive cases. BMC Cancer. 2011;11:85.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  13. , , , et al. Malignant melanoma in Taiwan: a prognostic study of 181 cases. Melanoma Res. 2004;14:537-41.
    [CrossRef] [PubMed] [Google Scholar]
  14. , , , et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19:3622-34.
    [CrossRef] [PubMed] [Google Scholar]
  15. , , , et al. Prognosis of acral melanoma: a series of 281 patients. Ann Surg Oncol. 2013;20:3618-25.
    [CrossRef] [PubMed] [Google Scholar]
  16. , , , . Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986-2005. Arch Dermatol. 2009;145:427-34.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  17. , , , et al. Acral lentiginous melanoma versus other melanoma: a single-center analysis in Japan. J Dermatol. 2017;44:932-8.
    [CrossRef] [PubMed] [Google Scholar]
  18. , , . Is the survival rate for acral melanoma actually worse than other cutaneous melanomas? J Dermatol. 2020;47:251-6.
    [CrossRef] [PubMed] [Google Scholar]
  19. , , , , , . Prognostic role of sentinel lymph node biopsy for patients with cutaneous melanoma: a retrospective study of surveillance, epidemiology, and end-result population-based data. Oncotarget. 2016;7:45671-7.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  20. , , , et al. The long-term prognostic impact of sentinel lymph node biopsy in patients with primary cutaneous melanoma: a prospective study with 10-year follow-up. Ann Surg Treat Res. 2018;95:286-96.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
  21. , , , et al. NRAS mutations in primary and metastatic melanomas of Japanese patients. Int J Clin Oncol. 2013;19:544-8.
    [CrossRef] [PubMed] [Google Scholar]
  22. , , . Prevalence of BRAF and NRAS mutations and a comparative analysis in primary and metastatic melanoma of Korea patients. Ewha Med J. 2014;37:30-5.
    [Google Scholar]
  23. , , , et al. Outcome of combination therapy using BRAF and MEK inhibitors among Asian patients with advanced melanoma: an analysis of 112 cases. Eur J Cancer. 2021;145:210-20.
    [CrossRef] [PubMed] [Google Scholar]
  24. , . Targeted therapy and immunotherapy for melanoma in Japan. Curr Treat Options Oncol. 2019;20:7.
    [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
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