Tang L, Wang YY, Lei HK, Wang CM, Teng Y, Xu QJ, Jiang QM, Chen B, Zeng XH, Guo BQ, Wang EW. Clinical characteristics and prognostic factors in patients with malignant melanoma: A Chinese prospective cohort study. World J Clin Oncol 2025; 16(6): 105813 [DOI: 10.5306/wjco.v16.i6.105813]
Corresponding Author of This Article
En-Wen Wang, PhD, Professor, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, No. 181 Han Yu Road, Shapingba District, Chongqing 400030, China. enwang313@cqu.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Long Tang, Chun-Mei Wang, Yan Teng, Xiang-Hua Zeng, Bian-Qin Guo, En-Wen Wang, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
Yi-Yao Wang, School of Medicine, Chongqing University, Chongqing 400044, China
Hai-Ke Lei, Qian-Jie Xu, Chongqing Cancer Multi-omics Big Data Application Engineering Research Center, Chongqing University Cancer Hospital, Chongqing 400030, China
Qing-Ming Jiang, Department of Pathology, Chongqing University Cancer Hospital, Chongqing 400030, China
Biao Chen, Department of Bone and Soft Tissue Tumor, Chongqing University Cancer Hospital, Chongqing 400030, China
Co-corresponding authors: Bian-Qin Guo and En-Wen Wang.
Author contributions: Wang EW, Tang L and Lei HK conceived the idea; Tang L wrote the manuscript; Wang EW and Guo BQ supervised the study; Tang L, Wang YY, Wang CM, Teng Y, Xu QJ, Jiang QM, Chen B, Zeng XH and Lei HK collected and analyzed data; Wang EW, Tang L and Guo BQ participated in the discussion. All authors have read and agreed to the published version of the manuscript. This study was jointly supervised by two senior investigators (Guo BQ and Wang EW), whose complementary expertise was indispensable to the project's success. Wang EW led the case collection, ethical review and statistical design, and her clinical experience provided a solid data base for this study. Guo BQ focused on the molecular mechanism of tumor, provided important data to be collected, participated in the experimental design, reviewed the results, and ensured the scientific rigor of the research conclusions. In addition, the interdisciplinary cooperation between the two professors promoted the depth and breadth of the research. Based on internationally accepted standards for corresponding authors (major contributions to research design, manuscript completion, and academic responsibility), both scholars participated in the conception, revision, and finalization of papers, and assume responsibility for funding and academic supervision. This division of labor was in line with the reality of multi-team collaborative research and demonstrated the academic value of collaborative research.
Supported by Natural Science Foundation of Chongqing, No. CSTB2023NSCQ-MSX0829.
Institutional review board statement: Members of the Ethics Committee carefully reviewed the submitted research protocol, researchers' qualifications and Application for exemption from informed consent through rapid review, and believed that the submitted materials basically met the ethical requirements.
Informed consent statement: Informed consent is documented in writing and signed by the patient or, if he or she does not have the capacity to sign, by a legal representative.
Conflict-of-interest statement: Authors declare no potential conflict of interests for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement:sharing statement: The data that support the findings of this study are available from the corresponding author, upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: En-Wen Wang, PhD, Professor, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, No. 181 Han Yu Road, Shapingba District, Chongqing 400030, China. enwang313@cqu.edu.cn
Received: February 8, 2025 Revised: March 24, 2025 Accepted: May 10, 2025 Published online: June 24, 2025 Processing time: 132 Days and 19.3 Hours
Abstract
BACKGROUND
Melanoma is a highly malignant tumor that has an extremely poor prognosis. It is the primary cause of death among cutaneous malignancies, accounting for 75% of such fatalities; approximately 325000 new cases and 57000 deaths were reported worldwide in 2020. The main modalities for melanoma treatment include surgery, immunotherapy, targeted therapy, high-dose interferon, antitumor angiogenesis, chemotherapy, and radiotherapy. Due to China's special national conditions, the main pathological types and therapeutic effects are greatly different from those in Europe and the United States, so more studies are needed to determine the curative effects of such treatments in the Chinese population.
AIM
To explore their clinical characteristics, prognostic influencing factors and real-world data to provide a reference basis for further diagnosis and treatment.
METHODS
We collected pathological data from patients diagnosed with malignant melanoma in our hospital in recent years. Univariate analysis was conducted using the log-rank test, while multivariate analysis was performed with the Cox proportional hazard regression model. The survival rate was calculated using the Kaplan-Meier method.
RESULTS
The male-to-female patient ratio was 1.04: 1. Among the clinical classifications, melanoma of the limb accounted for 47.56% of cases, followed by melanoma of the skin (18.18%) and mucosal melanoma (18.05%). The 5-year survival rates for stage I-II, stage III, and stage IV patients were 54.65%, 37.88%, and 28.58%, respectively. Univariate analysis revealed that age, tumor stage, treatment mode, platelet count at the first visit, and lactate dehydrogenase (LDH) level were significantly related to patient survival. Patients with high LDH and high platelet counts exhibited significantly lower survival rates at 1 year, 3 years, and 5 years. Multivariate analysis demonstrated that tumor stage, chemotherapy, interferon therapy, and LDH level were independent risk factors affecting patient survival and prognosis. Compared to the mortality rates of patients who did not receive chemotherapy or interferon therapy, those of patients who received chemotherapy and interferon therapy were 30.0% and 44.5% lower, respectively. Additionally, patients with elevated LDH levels were 2.27 times more likely to die than patients with normal LDH levels.
CONCLUSION
Melanoma is highly malignant, and its prognosis is influenced by numerous factors, resulting in an overall poor prognosis. This study identified several factors that impact patient prognosis, providing a foundation for individualized comprehensive treatment.
Core Tip: Melanoma is a highly malignant tumor that arises from melanocytes and has an extremely poor prognosis. This article collected and analyzed the clinical data of patients, several statistical methods were used to identify the factors that influence patient prognosis.
Citation: Tang L, Wang YY, Lei HK, Wang CM, Teng Y, Xu QJ, Jiang QM, Chen B, Zeng XH, Guo BQ, Wang EW. Clinical characteristics and prognostic factors in patients with malignant melanoma: A Chinese prospective cohort study. World J Clin Oncol 2025; 16(6): 105813
Melanoma, also known as malignant melanoma, is a highly malignant tumor that arises from melanocytes and has an extremely poor prognosis[1]. The early onset of the disease is mostly characterized by the appearance of a black lesion on the skin, deepening of pigmentation, and elevated subcutaneous nodules, and progression of the disease is characterized by the spread of lesions and the appearance of satellite-like damage[2]. It is the primary cause of death among cutaneous malignancies, accounting for 75% of such fatalities; approximately 325000 new cases and 57000 deaths were reported worldwide in 2020[3]. According to the clinical classification of the Chinese Society of Clinical Oncology (CSCO), melanoma can usually be classified into four types in China: cutaneous, acral, mucosal, and ocular. Approximately 95% of cutaneous melanoma occur in the Caucasian population[4]. On the other hand, the acral and mucosal types are more common in China, with approximately 50% of cases occurring in Chinese patients[5]. Previous studies have shown that mucosal melanoma accounts for 22.6% of all melanomas in China (118/522)[5]. Compared with cutaneous melanoma, mucosal melanoma is more prone to vascular invasion, postoperative recurrence, and a poor prognosis, with a 5-year overall survival (OS) rate of only 26.8%[6]. Currently, the main modalities for melanoma treatment include surgery, immunotherapy, targeted therapy, high-dose interferon, antitumor angiogenesis, chemotherapy, and radiotherapy. Among these, immunotherapy, targeted therapy and antiangiogenic drugs are the latest trends in drug therapy. Due to China's special national conditions, the main pathological types and therapeutic effects are greatly different from those in Europe and the United States, so more studies are needed to determine the curative effects of such treatments in the Chinese population. In this study, we collected relevant clinicopathological data and other related data from 759 patients with malignant melanoma treated at one cancer hospital over the past 4 years, single-center. We aimed to explore their clinical characteristics, prognostic influencing factors and real-world data to provide a reference basis for further diagnosis and treatment.
MATERIALS AND METHODS
Study population
A statistical analysis was conducted on 805 patients with pathologically confirmed malignant melanoma who were hospitalized at Chongqing University Cancer Hospital between January 1, 2017 and December 31, 2020. The disease codes were based on the International Classification of Diseases codes of the medical records room for the respective year. The inclusion criteria for the study were as follows: (1) Patients aged ≥ 18 years; (2) Patients who met the diagnostic criteria for melanoma in the Expert Consensus on Standardized Pathological Diagnosis of Melanoma in China (2017 version) and were histologically or cytologically confirmed to have malignant melanoma; and (3) Patients who were hospitalized. Patients who met any of the following criteria were excluded: (1) Patients with nonmalignant melanoma; (2) Patients who received outpatient treatment; (3) Patients without a pathological diagnosis; and (4) Patients with incomplete contact information. After exclusion, a total of 759 patients were included. The study adhered to the Declaration of Helsinki and was approved by the ethics committee. All the databases were protected for privacy and confidentiality.
Data collection
Patient demographic characteristics (such as age, sex, occupation, smoking history, etc.), disease information (including clinical stage, stage, treatment modality, etc.), test results [including platelet count, lactate dehydrogenase (LDH), etc.], and follow-up information were collected for analysis. Prognosis-related data, such as platelet count and LDH, were also collected. The Cox regression model was used for multifactor analysis, and variables were screened using the conditional forward method with a significance level of α = 0.20. Categorical variables were included in the model as dummy variables, with the first subgroup of each variable serving as the reference group. Other variables were directly included in the model for analysis.
Statistical analysis
Statistical analysis was performed using R4.2.2 software. Count data are expressed as absolute numbers (%), while data for continuous variables are expressed as the mean ± SD. Single-factor survival analysis was performed using the log-rank test, while multifactor analysis was conducted using the Cox proportional hazards regression model. The Kaplan-Meier method was used to calculate the survival rate. The test level α was set to 0.05, and P < 0.05 was considered to indicate statistical significance.
RESULTS
Clinical characteristics of patients
The male-to-female patient ratio was 1.04:1. Most patients were between 50 and 70 years old, accounting for 53.23% of the cohort. Acral type melanoma was the most frequent clinical type, accounting for 47.56%, followed by cutaneous type melanoma (18.18%), mucosal melanoma (18.05%), ocular type melanoma (4.35%), and melanoma of unknown primary site (11.86%). Among cases of mucosal melanoma, nearly half had a primary origin in the nasal cavity (47.44%), followed by the gastrointestinal tract (20.44%), oral cavity (17.52%), vagina (5.84%), and other sites (8.76%). A total of 23 patients, accounting for 3.03%, also had other types of tumors. Of all patients, 172 (29.25%) had stage I-II disease, 166 (28.23%) had stage III disease, and 250 (42.52%) had stage IV disease. Surgical treatment was given to 69.96% of the patients, and surgery was the main treatment modality. At initial diagnosis, 17.65% of patients had increased LDH levels, as shown in Table 1.
Table 1 Clinical characteristics of patients with malignant melanoma.
Patients were followed up after discharge using various methods, such as telephone and WeChat. The follow-up schedule included visits every six months for the first two years after discharge and at least once a year thereafter. The follow-up cutoff date was December 31, 2022. The analysis indicated that age, stage, and surgery were the main factors affecting patient survival. Patients with stage I-II disease had a mean survival time of 68.03 months (95%CI: 59.42-76.64), those with stage III disease had a mean survival time of 52.34 months (95%CI: 43.72-60.97), and those with stage IV disease had a mean survival time of 33.85 months (95%CI: 28.46-39.23), with 5-year survival rates of 54.65%, 37.88%, and 28.58%, respectively. Univariate analysis revealed that age, stage, treatment modality, platelet count at initial diagnosis, and LDH level were significantly associated with patient survival. Patients with high LDH levels and platelet counts had significantly lower survival rates at 1, 3, and 5 years, as shown in Table 2.
Table 2 Univariate analysis of prognostic factors in patients with malignant melanoma.
Variable
Number of death (%)
Mean survival (months) (95%CI)
Median survival (months) (95%CI)
Survival rate (%)
χ2
P value
1 year
3 years
5 years
Age (years)
17.757
< 0.001
≤ 50
65 (31.55)
57.65 (50.06, 65.24)
87.3 (35.31, 139.29)
78.80
61.03
52.87
51-70
159 (39.36)
50.28 (44.99, 55.57)
37.4 (28.56, 46.24)
77.00
51.92
39.31
≥ 71
74 (49.66)
32.06 (26.17, 37.96)
20.6 (11.26, 29.94)
76.11
36.70
14.68
Sex
0.000
0.988
Female
147 (39.41)
50.07 (44.51, 55.64)
37.4 (28.94, 45.86)
75.14
52.51
39.68
Male
151 (39.12)
48.36 (43.28, 53.44)
37.4 (26.74, 48.06)
79.01
50.75
37.80
Marriage
1.512
0.219
Married
270 (38.74)
51.05 (47.02, 55.09)
37.4 (30.31, 44.49)
77.48
52.64
52.64
Others
28 (45.16)
40.74 (29.29, 52.19)
32.6 (14.22, 50.98)
71.11
42.10
31.57
Ethnicity
0.003
0.960
Han
289 (39.11)
49.6 (45.53, 53.67)
37.4 (30.94, 43.86)
77.09
52.00
38.91
Others
9 (45.00)
46.73 (28.89, 64.58)
15.8 (0, 0)
71.79
47.86
47.86
Types of health insurance
3.290
0.193
Resident health insurance
163 (39.76)
49.98 (44.82, 55.13)
37.6 (29.2, 46)
76.98
52.74
36.35
Employee health insurance
87 (42.23)
44.17 (37.26, 51.08)
29 (17.3, 40.7)
73.27
44.50
37.15
Self-funded and others
48 (33.57)
50.99 (43.58, 58.4)
59.9 (0, 0)
81.06
56.68
45.30
Clinical type classification
4.172
0.383
Cutaneous
49 (35.51)
49.74 (42.04, 57.43)
47.7 (28.89, 66.51)
77.93
57.12
38.88
Acral
135 (37.4)
49.09 (43.74, 54.45)
37 (28.86, 45.14)
82.51
50.95
37.34
Mucosal
59 (43.07)
49.05 (40.16, 57.94)
36.4 (20.62, 52.18)
68.52
48.93
39.63
Ocular
16 (48.48)
42.6 (27.18, 58.01)
27.7 (0, 67.66)
62.04
47.27
31.51
Types of undetermined origin
39 (43.33)
43.22 (34.05, 52.39)
29 (10.84, 47.16)
66.11
45.08
34.88
Combined with other tumors
0.027
0.870
No
289 (39.27)
49.55 (45.39, 53.71)
37.4 (30.44, 44.36)
77.07
51.63
38.77
Yes
9 (39.13)
47.75 (28.64, 66.86)
35.5 (12.09, 58.91)
78.94
48.58
36.43
Underlying Diseases
7.586
0.006
No
238 (38.08)
52.26 (47.85, 56.67)
41 (34.35, 47.65)
77.68
54.93
41.70
Yes
60 (44.78)
33.79 (27.1, 40.47)
22.9 (13.43, 32.37)
71.63
33.97
19.51
Tumor stage
52.591
< 0.001
Ⅰ-Ⅱ
38 (22.09)
68.03 (59.42, 76.64)
0 (0, 0)
88.31
69.98
54.65
Ⅲ
53 (31.93)
52.34 (43.72, 60.97)
43.1 (29.83, 56.37)
82.02
53.95
37.88
Ⅳ
125 (50.00)
33.85 (28.46, 39.23)
15.1 (11.71, 18.49)
58.04
36.67
28.58
Surgical operation
18.223
0.000
No
118 (51.75)
39.6 (33.46, 45.74)
25.9 (18.66, 33.14)
69.78
41.02
26.25
Yes
180 (33.90)
53.42 (48.62, 58.23)
46.2 (33.23, 59.17)
79.77
56.56
44.09
Radiotherapy
0.010
0.921
No
244 (37.95)
49.6 (45.49, 53.7)
37.3 (29.91, 44.69)
77.11
52.14
38.69
Yes
54 (46.55)
47.83 (39.23, 56.44)
37.8 (24.61, 50.99)
76.17
50.86
39.29
Chemotherapy
3.054
0.081
No
192 (39.92)
45.07 (40.43, 49.71)
34 (28.27, 39.73)
76.92
48.32
33.86
Yes
106 (38.13)
54.8 (48.55, 61.06)
43.1 (27, 59.2)
76.52
56.53
44.52
Immunotherapy
1.637
0.441
No
264 (41.64)
50.25 (46.07, 54.44)
37.6 (30.82, 44.38)
77.01
52.81
39.28
Yes
34 (27.42)
28.44 (23.16, 33.71)
23 (15.5, 30.5)
73.91
39.06
39.06
Targeted therapy
1.042
0.594
No
290 (39.84)
49.58 (45.5, 53.67)
37.3 (30.73, 43.87)
76.86
51.62
38.32
Yes
8 (26.67)
52.36 (34.14, 70.58)
80.5 (0, 0)
76.06
57.04
57.04
Use of interleukins
0.877
0.645
No
276 (38.82)
49.67 (45.47, 53.87)
37.3 (30.33, 44.27)
76.60
51.46
39.24
Yes
22 (46.81)
46.19 (35.54, 56.84)
39.5 (25.55, 53.45)
83.72
52.64
19.19
Use of interferon
3.320
0.068
No
265 (40.03)
46.94 (42.73, 51.15)
36.9 (29.84, 43.96)
75.77
51.00
37.53
Yes
33 (34.38)
58.46 (48.01, 68.9)
59.9 (35.1, 84.7)
84.27
57.77
46.36
Use of antiangiogenic drugs
0.796
0.672
No
284 (39.23)
49.63 (45.53, 53.73)
37.3 (30.54, 44.06)
77.67
51.53
39.07
Yes
14 (41.18)
45.6 (31.17, 60.04)
39.8 (14.15, 65.45)
65.42
50.10
41.75
Platelet count
16.627
< 0.001
Normal
245 (37.98)
49.8 (45.27, 54.32)
37.4 (29.97, 44.83)
78.13
52.27
38.93
Low
30 (40.00)
55.91 (44.92, 66.9)
42.9 (0, 0)
75.13
54.27
48.24
High
14 (50.00)
16.57 (9.99, 23.16)
10.5 (5.35, 15.65)
38.93
29.20
29.20
Lactate dehydrogenase
50.549
< 0.001
Normal
169 (34.28)
53 (48.26, 57.73)
44.6 (31.79, 57.41)
83.14
57.15
43.64
Low
2 (33.33)
43.96 (27.04, 60.88)
42.9 (0, 86.94)
80.00
40.00
40.00
High
70 (52.24)
30.07 (21.38, 38.77)
12.4 (7.35, 17.45)
50.99
29.40
16.38
Multifactorial analysis of factors affecting prognosis
The results of the multifactorial analysis revealed that stage, LDH levels, chemotherapy and interferon therapy were independent risk factors that affected patient survival. It can be concluded that the risk of death in patients with stage IV disease is 3.03 times greater than that in patients with stages I-II disease. Furthermore, compared to patients who did not receive chemotherapy or interferon therapy, patients who received chemotherapy or interferon therapy had a 30.0% and 44.5% lower risk of death, respectively. Finally, patients with elevated LDH levels had a 2.27-fold greater risk of death than those with normal LDH levels, as shown in Table 3.
Table 3 Multifactor analysis of factors affecting prognosis in patients with malignant melanoma.
Variable
β
SE
Wald
P value
HR (95%CI)
Tumor stage
31.402
0.000
Ⅰ-Ⅱ
1
Ⅲ
0.459
0.232
3.912
0.048
1.582 (1.004-2.492)
Ⅳ
1.107
0.211
27.455
0.000
3.025 (1.999-4.576)
Chemotherapy (control group = no)
-0.362
0.158
5.239
0.022
0.696 (0.511-0.949)
Interferon therapy (control group = no)
-0.588
0.240
5.999
0.014
0.555 (0.347-0.889)
Lactate dehydrogenase
23.638
0.000
Normal
1
Low
0.788
0.728
1.172
0.279
2.199 (0.528-9.163)
High
0.819
0.171
22.825
0.000
2.267 (1.621-3.172)
Survival curves were generated for variables that significantly correlated with survival in the multifactorial analysis. The results indicated that patients with stage IV disease had the worst prognosis, while patients with normal or reduced levels of LDH had a better prognosis than those with elevated levels. Furthermore, patients treated with chemotherapy and interferon had a better prognosis than those who did not receive treatment. These findings are illustrated in Figure 1.
Figure 1 Kaplan-Meier survival curves for different patient groups.
A: Tumor stage; B: Level of lactate dehydrogenase; C: Interferon therapy; D: Chemotherapy.
DISCUSSION
Melanoma is a major cause of skin cancer-related death in developed countries, and its incidence has been increasing in China over the past three decades[7]. The introduction of immunotherapy and targeted therapy has improved the prognosis of malignant melanoma, but the efficacy of different treatments varies among populations due to racial differences, making it necessary to establish evidence-based guidelines for Chinese patients. In this study, we analyzed the clinical data of 759 patients with malignant melanoma treated at our hospital; approximately half of the patients had the acral type, followed by the cutaneous and mucosal types, which is consistent with the findings reported in China[5]. Interestingly, we found that the number of patients whose tumors originated from the right side of the body was greater than that of those whose tumors originate from the left side. Among cases of melanoma of the nasal mucosa, 63.02% originated from the right side of the nasal cavity, and only 36.92% originated from the left side. A similar phenomenon was observed in melanoma of the extremities, with 54.02% of cases occurring in the right extremity and 45.98% in the left extremity. The cause of this asymmetry remains unclear and warrants further investigation. However, this study has limitations, as the data were collected in recent years, and some patients are still alive. Immunotherapeutic drugs, such as ipilimumab and pembrolizumab, have been gradually applied in the clinic and were first applied in our hospital in 2017, and the two-drug combination therapy program of trametinib combined with darafenib was not approved for the market in China until the end of 2019. Additionally, the initial price was high, and these drugs are not covered by medical insurance, so relatively few patients utilized this treatment. The increasing use of immunotherapy and targeted drugs may have biased the results of the survival analysis. Only 124 patients accepted immunotherapy, and 30 patients accepted targeted therapy because immunotherapy and targeted drugs were not widely available in the region. Due to the limitations of single-center clinical study, there are issues of selection bias and applicability of the findings to a broader population. In further studies, this limitation can be minimized by adding more patients from multiple centers in different regions. This study may result in absent data or discrepancies, for samples with more than 10% missing data, we chose not to include them in the study; for samples with less than 10% missing data, we used the mean of the missing variable for imputation.
Melanoma is known to be one of the most immunogenic tumors, with high levels of immune cell infiltration in cutaneous melanoma. However, the response rates to immunotherapy in China are lower than those reported in Europe and the United States, primarily due to the predominance of acral and mucosal melanomas, which exhibit low PD-L1 expression and a low tumor mutation load[8]. In our study, the acral type accounted for nearly half of the cases, while the cutaneous type accounted for only 18.18%, which differs greatly from the 95% reported in other countries[4]. A previous study showed that the median progression-free survival (PFS) of Chinese patients receiving pembrolizumab monotherapy for advanced or metastatic melanoma was 2.8 months, the median OS was 12.1 months, and the objective response rate (ORR) was 16.7%, which is much lower than that reported in Europe and the United States[9,10]. The SWOGS1801 phase II trial divided stage IIIB to IVC patients into pabrolizumab neoadjuvant-adjuvant and pabrolizumab adjuvant-only groups with a median follow-up of 14.7 months. The results showed that the 2-year event-free survival rates of patients in the neoadjuvant-adjuvant and adjuvant-only groups were 72% (95%CI 64% to 80%) and 49% (95%CI 41% to 59%), respectively[11]. However, the study included few cases of the limb and mucosal subtypes, so the reliability of PD-1 for these two types of melanoma needs to be further explored. Only 16.34% of patients in our study used immunotherapy due to drug accessibility, and no statistically significant difference was observed in the prognosis of patients who received or did not receive immunotherapy. This may be related to the limited sample size and the greater proportion of patients with acral melanomas in the Chinese population.
The development of melanoma is an extremely complex pathophysiological process, with one of the main mechanisms being the activation of oncogenes and inactivation of tumor suppressor genes, leading to abnormalities in multiple signaling pathways. This eventually results in the uncontrolled proliferation and metastasis of melanocytes. The RAS-RAF-MEK-ERK pathway plays an important role; BRAF V600E is the most common type of melanoma gene mutation, and there are different mutation rates between Caucasians and Asians. Studies have shown that the rate of BRAF gene mutation in Caucasian patients with melanoma is greater than 60%[12]. A recent single-center study in China showed that the BRAF gene mutation rate was 24.0% in 691 melanoma patients, with V600E mutations predominating (87.3%)[13]. The BRAF gene mutation results in activation of the BRAF-MAPK/ERK kinase (MEK)-extracellular regulatory protein kinase (ERK1/2) pathway. The use of BRAF inhibitors, such as vemurafenib, dabrafenib and the MEK inhibitor trametinib, can greatly improve prognosis and prolong survival; moreover, the treatment response rate is high, and adverse effects are low[14,15]. However, COHEN et al[16] showed that 10% to 15% of melanoma patients exhibit resistance to BRAF inhibitors, and this was mainly observed among melanoma patients with BRAF mutations. Tunlametinib (HL-085) is a noncompetitive MEK inhibitor of ATP for NRAS mutations[17] and is well tolerated[18]. According to the 2022 CSCO guidelines, HL-085 is a class III agent recommended for second-line treatment of cutaneous, limbic, and mucosal melanoma patients with NRAS mutations. The 2023 CSCO guideline update moved it forward to a second-line class I recommendation. Mucosal melanoma c-Kit gene mutations are reported to be significantly more prevalent in mucosal melanoma than in cutaneous melanoma and indicate a poor prognosis[19,20]. KIT mutations and/or amplification are more common in acral melanomas than in other types of melanoma (10%-20%)[21]. Currently, common KIT inhibitors include imatinib, sunitinib, dasatinib, and nilotinib[22], and only imatinib and nilotinib have fair efficacy in treating acral melanoma. A retrospective analysis of 78 patients with metastatic melanoma harboring a c-Kit mutation or amplification (42 patients with the limbal type) treated with imatinib revealed a median OS and PFS of 13.1 and 4.2 months, respectively, and an ORR and disease control rate of 21.8% and 60.3%, respectively[23]. Most of the patients in this study were not treated with relevant targeted drugs due to drug accessibility, but the median survival time of patients treated with targeted therapy was significantly longer than that of nonusers, and their morbidity and mortality rates were lower (26.67% vs 39.84%), which proves, to some extent, the effectiveness of targeted therapy.
Blood LDH is thought to be associated with the prognosis of patients with melanoma. LDH is not an actively secreted enzyme; it is only released upon cell death and is significantly elevated in many patients with malignancies. LDH levels are one of the prognostic factors for melanoma and have been used in the American Joint Committee on Cancer melanoma staging system for more than a decade. Although the specificity of LDH levels as a biomarker for melanoma increases with increasing stage, reaching up to 92% in stage IV, the sensitivity decreases with increasing stage, dropping to 79% in stage IV[24]. The American Cancer Society estimated that the largest absolute survival difference between black and white patients with cancer was among melanoma patients, with a decrease of approximately 25% in black patients[25]. In one study[26], of 334 patients with cutaneous melanoma, 150 (44.9%) had normal LDH, 112 (33.5%) had LDH < 1.5 × upper limit of normal (ULN), 57 (17.1%) had LDH 1.5 to 10 × ULN, and 15 (4.5%) had LDH > 10 × ULN. In race subgroup analysis, in the LDH > 10 × UL group, black patients accounted for the highest proportion (13.3%), indicating that the effect of LDH level on the prognosis of melanoma was related to demographic characteristics. The results of this study showed that 134 patients with elevated LDH, including 67.91% of stage IV patients, had 100% specificity in stage IV patients. Patients with normal or reduced LDH levels had a better prognosis than those with elevated levels, and the proportion of patients with elevated LDH levels was lower, which is generally consistent with data from foreign studies.
CONCLUSION
Melanoma is a highly malignant disease, and its prognosis is affected by a variety of factors, resulting in a poor overall prognosis. By analyzing the clinical characteristics of 759 melanoma patients in one hospital, this study identified several factors that affect the prognosis and provides a basis for individualized and comprehensive treatment. Surgery remains the preferred and most effective treatment for melanoma patients, and with the increasing availability of immunotherapy and targeted drugs, further exploration of stratification factors, such as the primary site, type of gene mutation, and type of immunotherapeutic agent, is needed to provide a reference for evidence-based treatment.
ACKNOWLEDGEMENTS
We thank professor Wang EW, the co-corresponding author of this article, for her support and guidance in this study, as well as all other doctors who participated in this study.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade A, Grade D
Novelty: Grade B, Grade D
Creativity or Innovation: Grade B, Grade D
Scientific Significance: Grade A, Grade D
P-Reviewer: Imbeah EG; Mukundan A S-Editor: Qu XL L-Editor: A P-Editor: Zhang XD
Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH Jr, Lao CD, Linette GP, Thomas L, Lorigan P, Grossmann KF, Hassel JC, Maio M, Sznol M, Ascierto PA, Mohr P, Chmielowski B, Bryce A, Svane IM, Grob JJ, Krackhardt AM, Horak C, Lambert A, Yang AS, Larkin J. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.Lancet Oncol. 2015;16:375-384.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 1853][Cited by in RCA: 2092][Article Influence: 209.2][Reference Citation Analysis (0)]
Wang X, Luo Z, Chen J, Chen Y, Ji D, Fan L, Chen L, Zhao Q, Hu P, Sun P, Jia Z, Guo J, Si L. First-in-human phase I dose-escalation and dose-expansion trial of the selective MEK inhibitor HL-085 in patients with advanced melanoma harboring NRAS mutations.BMC Med. 2023;21:2.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in RCA: 11][Reference Citation Analysis (0)]
Zhao Q, Wang T, Wang H, Cui C, Zhong W, Fu D, Xi W, Si L, Guo J, Cheng Y, Tian H, Hu P. Phase I pharmacokinetic study of an oral, small-molecule MEK inhibitor tunlametinib in patients with advanced NRAS mutant melanoma.Front Pharmacol. 2022;13:1039416.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Reference Citation Analysis (0)]
Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, Corless CL, Li L, Li H, Sheng X, Cui C, Chi Z, Li S, Han M, Mao L, Lin X, Du N, Zhang X, Li J, Wang B, Qin S. Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification.J Clin Oncol. 2011;29:2904-2909.
[RCA] [PubMed] [DOI] [Full Text][Cited by in Crossref: 502][Cited by in RCA: 473][Article Influence: 33.8][Reference Citation Analysis (0)]
Stark MS, Klein K, Weide B, Haydu LE, Pflugfelder A, Tang YH, Palmer JM, Whiteman DC, Scolyer RA, Mann GJ, Thompson JF, Long GV, Barbour AP, Soyer HP, Garbe C, Herington A, Pollock PM, Hayward NK. The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue and Serum: A MicroRNA Expression Analysis.EBioMedicine. 2015;2:671-680.
[RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)][Cited by in Crossref: 63][Cited by in RCA: 80][Article Influence: 8.0][Reference Citation Analysis (0)]
