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The choice of adjuvant radiotherapy in adrenocortical carcinoma patients after radical adrenalectomy: a population-based analysis
Minjuan He1 and Minqin He2* İD
*Correspondence: Minqin He Hmqing2025@163.com 1Department of Endocrinology, The First People’s Hospital of Jiashan County, Jiaxing 314100, Zhejiang China
2Department of Hyperbaric Oxygen, The Second Hospital of Jiaxing City, No.1518, Huancheng North Road, Nanhu, Jiaxing 314001, Zhejiang, China
Abstract
Purpose This study aimed to more accurately screen the adrenocortical carcinoma(ACC) patients who would benefit from adjuvant radiotherapy after radical adrenalectomy.
Methods The clinicopathological data from 2000 to 2018 were downloaded from the SEER database. All patients were divided into two groups: surgery alone and surgery followed by radiotherapy. A propensity score-matched(PSM) pair analysis was performed to reduce potential selection bias. The Chi-square test examined differences between groups. Univariate and multivariate analyses were applied to identify prognostic factors affecting patient survival. Kaplan-Meier analysis estimated the two groups’ overall survival (OS).
Results 636 ACC patients who underwent radical adrenalectomy were enrolled. Among them, 95 patients (14.94%) had undergone adjuvant radiotherapy, whereas 541 (85.06%) received surgery only. After PSM, 89 received adjuvant radiotherapy, and 89 received surgery alone. Before PSM, the patients did not benefit from adjuvant radiotherapy, while the OS of the adjuvant radiotherapy group was better than that of surgery alone after PSM(P=0.028). Univariate Cox regression analysis showed that radiotherapy, sex, tumor size, disease stage, grade, and lymph node status were correlated with OS. Multivariable Cox regression analysis demonstrated that age, disease stage, lymph node status, and adjuvant radiotherapy influenced overall survival. Patients were risk-stratified based on known high-risk features for relapse or death; the adjuvant radiotherapy was significantly associated with more prolonged survival(P=0.031) in the high-risk group but not the low-risk group.
Conclusion Our study shows that ACC patients after radical adrenalectomy could benefit from adjuvant radiotherapy, especially in high-risk patients. So, we can take ACC patients after radical adrenalectomy and with more high-risk features(risk factor ≥2) as a potential beneficiary of adjuvant radiotherapy.
Keywords Adrenocortical carcinoma, Radical adrenalectomy, Adjuvant radiotherapy, SEER, Overall survival
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1 Introduction
Adrenocortical carcinoma(ACC) is one of the aggressive Malignancies with a dismal prognosis, and the 5-year survival for ACC Patients in stage IV disease is only 13% [1, 2]. Surgical resection offers the only potentially curative treatment, but there is a high postoperative recurrence rate; furthermore, many patients can not receive early diag- nosis and treatment due to its complex and varied clinical manifestations and unappar- ent early symptoms [3]. Currently, the primary therapies for patients with postoperative recurrence or advanced disease are mitotane and chemotherapy; However, the thera- peutic effect is still not satisfactory because the disease remission rate is only about 23%, and the median progression-free survival (PFS) has proved to be only 5.0 months [4]. In addition, a high dosage of mitotane was required to keep its plasma treatment con- centration, which might result in significant and severe side effects in the gastroenteric, nervous, and endocrine systems [5].
Postoperative adjuvant radiotherapy(RT) is an important component of the compre- hensive treatment strategies of ACC, but controversy over the efficacy of radiotherapy remains. In some studies, postoperative RT significantly improved local control and pal- liated local symptoms such as pain due to osseous metastases compared with those who received surgical treatment alone. However, there was no significant difference in overall survival(OS) and recurrence-free survival(RFS) [6, 7]. In other studies, adjuvant radio- therapy was an independent protective factor for overall survival, significantly improv- ing ACC patients’ OS and disease-free survival (DFS) after surgical resection [8, 9]. The role of adjuvant radiotherapy in ACC patients after complete resection is not definite, and which patient subgroups benefit most from adjuvant radiotherapy remains unclear, too.
Based on this background, this study aimed to compare treatment outcomes for ACC patients receiving radical surgery followed by adjuvant radiotherapy versus radi- cal surgery alone by using the Surveillance, Epidemiology, and End Results (SEER) database(www.seer.cancer.gov). We sought to identify the clinical characteristics of patients who may most likely benefit from adjuvant radiotherapy to inform clinical decision-making.
2 Patients and methods
2.1 Study population
The clinicopathological data of ACC patients from 2000 to 2018 were downloaded from the SEER database using SEER*Stat 8.4.4. The data collected from 17 cancer registries were released in April 2024 and were based on the November 2023 submission. The inclusion criteria were as follows: (1) The primary site of the tumor was C74.0 with his- tologic type code 8010, 8140, and 8370, or C74.9 with histologic type code 8370; (2) All patients underwent radical adrenalectomy with surgical code 40 [total surgical removal of primary site] or 60 [radical surgery]; (3) ACC as the first primary malignancy or the only primary tumor and all diagnoses were verified by histology; (4) All patients were ≥18 years of age and had unilateral tumors at the same time. Exclusion criteria included the following: (1) Information on radiotherapy was unknown or received preoperative or intraoperative radiotherapy; (2) Missing baseline characteristics, including race, dis- ease stage, tumor size, and death, but the cause of death is unclear; (3) Died within 3 months after surgery or age < 18 years. All patients were divided into two groups based
on whether they received postoperative radiotherapy: surgery alone and surgery fol- lowed by radiotherapy (surgery + radiation). The patient flow chart is detailed in Fig. 1. Because the SEER is a publicly available database, all patient data were anonymous, and our hospital ethics committee exempted ethics approval.
2.2 Clinical variables
Study variables included age, sex, race, laterality, tumor size, disease stage, lymph node status, grade, adjuvant therapy (chemotherapy or radiotherapy), survival time, and sur- vival status. Race was grouped into white and other. Age was divided into two groups of ≤60 and >60 years. Tumor sizes were divided into ≤10 cm and >10 cm. Lymph node status was divided into negative, positive, and unknown. The tumor grade was split into I+ II (well and medium differentiated) and III + IV (poorly and undifferentiated). Adju- vant therapy was classified as adjuvant chemotherapy, yes or no/unknown, or radio- therapy, yes/no. The primary outcome was OS of ACC patients who underwent radical adrenalectomy, and the OS refers to the period from diagnosis until death or the last follow-up date.
2.3 Statistical analysis
Data processing and analysis were performed using R version 4.4.0 (2024-04-24), along with Zstats 1.0 (www.zstats.net). All variables were transformed into categorical vari- ables. The clinicopathological characteristics between the surgery + radiation and sur- gery alone groups were analyzed using the Chi-square test. Univariate and multivariate robust Cox proportional hazards regression models were used to examine the inde- pendent effects of adjuvant radiotherapy and other covariates on survival. The log-rank test was used to compare survival outcomes between the two groups, and following the
Patients diagnosed with adrenocortical carcinoma between 2000 and 2018 in SEER database (n=1697)
Excluded (n=1061):
Not the first primary malignant tumor(n=212)
Not performed radical adrenalectomy(n=713)
Information on radiotherapy was unknown
or received preoperative or intraoperative radiotherapy(n=7)
636 patients were enrolled in this study
The follow-up time was less than 3 months or unclear, or the cause of death was unknown(n=52) Unknown disease stage, laterality, tumor size, race, or age <18(n=77)
Surgery Alone(n=541)
Surgery+Radiation(n=95)
178 patients were enrolled after PSM
Surgery Alone(n=89)
Surgery+Radiation(n=89)
Kaplan-Meier(KM) methodology, the survival curves were plotted. The P <0.05 was con- sidered statistically significant.
A propensity score-matched(PSM) pair analysis was performed to counteract the imbalance in baseline characteristics between the two groups and to prevent potential selection bias. The PSM analysis included all the significantly different variables (P<0.05) in baseline characteristics. The (1:1) nearest neighbor Matching method Matched base- line characteristics between the two groups, and the caliper was 0.05. A total of 636 ACC patients were enrolled in the study before PSM; after PSM, 178 patients were included for further survival analysis.
2.4 Exploratory analyses
According to the European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults and NCCN Clinical Practice Guidelines in Oncology (NCCN Guideline), and combining the available data in the SEER database, advanced age, lymph node status positive, advanced disease stages, large tumor diameter(>10 cm), and histological differentiation poor were considered as high- risk features for relapse or death in adult ACC patients [10, 11]. Based on these high-risk features, patients were divided into the low-risk group (risk factor ≤ 1) and the high-risk group (risk factor ≥ 2). We intend to conduct an exploratory analysis to identify which risk subgroup might benefit from adjuvant radiotherapy.
3 Results
3.1 Patient characteristics
Based on the inclusion and exclusion criteria, 636 primary ACC patients who underwent radical adrenalectomy met the inclusion criteria. Among them, 95 patients (14.94%) had undergone adjuvant radiotherapy, whereas 541 (85.06%) received surgery only. The two groups had no significant differences regarding age, race, laterality, tumor size, grade, or lymph node status. However, the gender distribution was different (p=0.015); further- more, patients with advanced disease(65.26% vs. 48.61%; P=0.011) or who received che- motherapy(63.16% vs. 36.41%;p<0.001) are more likely to receive adjuvant radiotherapy.
After PSM, the groups showed no significant differences concerning sex, disease stage, or Chemotherapy. 178 patients were included for further survival analysis; 89 received postoperative adjuvant radiotherapy, and 89 received surgery alone. The clinical and pathologic characteristics of the adjuvant radiotherapy after surgery group and the sur- gery alone group patients before and after PSM are shown in Table 1. The density plot of the logit of the propensity score before and after PSM is shown in Fig. S1.
3.2 Survival analysis
Among the 636 patients, 402 patients(63.21%) died during the follow-up, and the median survival time was 52.00 months (95%CI, 42.13-63.88 months). All patients’ 1-, 3-, and 5-year overall survival rates were 81.7%, 56.6% and 46.7%. In the surgery alone group, they were 82.2%, 56.7%,and 46.9% with 52.00 month median survival time(95%CI,39.43-64.57 months), whereas in postoperative adjuvant radiotherapy group were 78.7%, 56.5%,and 45.2% with 48.00 month median survival time(95%CI,19.47-76.53 months). The KM survival analysis result indicates that compared with surgery alone, postoperative adjuvant radiotherapy did not confer a survival benefit(P=0.758; Fig. 2A).
| Variable | Before PSM | P | After PSM | P | ||
|---|---|---|---|---|---|---|
| Surgery Alone | Surgery + Radiation | Surgery Alone | Surgery + Radiation | |||
| n (%) | n (%) | n (%) | n (%) | |||
| Total, n | 541 | 95 | 89 | 89 | ||
| Age | 0.169 | 1.00 | ||||
| ≤60 y | 372 (68.76) | 72 (75.79) | 66 (74.16) | 66 (74.16) | ||
| >60 y | 169 (31.24) | 23 (24.21) | 23 (25.84) | 23 (25.84) | ||
| Sex | 0.015 | 0.881 | ||||
| Female | 339 (62.66) | 47 (49.47) | 45 (50.56) | 46 (51.69) | ||
| Male | 202 (37.34) | 48 (50.53) | 44 (49.44) | 43 (48.31) | ||
| Race | 0.640 | 0.410 | ||||
| White | 460 (85.03) | 79 (83.16) | 77 (86.52) | 73 (82.02) | ||
| Other | 81 (14.97) | 16 (16.84) | 12 (13.48) | 16 (17.98) | ||
| Laterality | 0.090 | 0.881 | ||||
| Left | 307 (56.75) | 45 (47.37) | 43 (48.31) | 44 (49.44) | ||
| Right | 234 (43.25) | 50 (52.63) | 46 (51.69) | 45 (50.56) | ||
| Tumor size | 0.113 | 0.337 | ||||
| ≤10 cm | 235 (43.44) | 33 (34.74) | 26 (29.21) | 32 (35.96) | ||
| >10 cm | 306 (56.56) | 62 (65.26) | 63 (70.79) | 57 (64.04) | ||
| Disease stage | 0.011 | 0.689 | ||||
| Localized | 278 (51.39) | 33 (34.74) | 27 (30.34) | 31 (34.83) | ||
| Regional | 153 (28.28) | 36 (37.89) | 32 (35.96) | 33 (37.08) | ||
| Distant | 110 (20.33) | 26 (27.37) | 30 (33.71) | 25 (28.09) | ||
| Grade | 0.999 | 0.405 | ||||
| I+II | 52 (9.61) | 9 (9.47) | 6 (6.74) | 8 (8.99) | ||
| III+ IV | 91 (16.82) | 16 (16.84) | 22 (24.72) | 15 (16.85) | ||
| Unknown | 398 (73.57) | 70 (73.68) | 61 (68.54) | 66 (74.16) | ||
| Lymph node | 0.282 | 0.958 | ||||
| status | ||||||
| Negative | 105 (19.41) | 25 (26.32) | 21 (23.60) | 21 (23.60) | ||
| Positive | 37 (6.84) | 7 (7.37) | 7 (7.87) | 6 (6.74) | ||
| Unknown | 399 (73.75) | 63 (66.32) | 61 (68.54) | 62 (69.66) | ||
| Chemotherapy | <0.001 | 0.760 | ||||
| No/Unknown | 344 (63.59) | 35 (36.84) | 37 (41.57) | 35 (39.33) | ||
| Yes | 197 (36.41) | 60 (63.16) | 52 (58.43) | 54 (60.67) | ||
A
B
1.00
Treatment- Surgery Alone- Surgery+Radiation
1.00-
Treatment-
Surgery Alone
Surgery+Radiation
Overall Survival (%)
0.75-
Log rank P = 0.758 HR (95%CI): 1.047 (0.787 - 1.392)
Overall Survival (%)
0.75-
Log rank P = 0.028 HR (95%CI): 0.667 (0.464 - 0.959)
0.50
0.50
0.25
0.25
0.00
0.00
0
30
60
90
120
150
180
210
240
270
0
30
60
90
120 Survival Months
50
180
210
240
270
Survival Months
Number at risk
Number at risk
541
338
215
152
119
93
63
46
21
0
-
89
48
20
13
7
6
5
2
2
0
95
54
30
19
9
4
2
1
1
0
1
89
51
28
18
5
3
2
1
1
0
After PSM, the median survival time was 33.00 months (95%CI, 23.94-42.07 months) in the surgery alone group, whereas in the postoperative adjuvant radiotherapy group was 48.00 months (95%CI, 28.74-67.26 months), meaning that patients treated with postop- erative adjuvant radiotherapy could obtain more survival benefit than patients receiving surgery alone(P=0.028; Fig. 2B).
Univariate Cox regression analysis showed that radiotherapy, sex, tumor size, disease stage, grade, and lymph node status were significantly correlated with OS (P<0.05). At the same time, age, race, laterality, and chemotherapy were not(P>0.05). After adjust- ment for confounding factors in a multivariate Cox regression analysis, age(HR, 1.631; 95%CI, 1.038-2.564; P=0.034), disease stage(HR, 2.687; 95%CI, 1.616-4.466; P<0.001), and lymph node status(HR, 3.165; 95%CI, 1.349-7.426; P=0.008) were independently associated with poorer survival. Meanwhile, after adjusting for other clinical features, adjuvant radiotherapy was an independent protective factor for OS in ACC patients who underwent radical adrenalectomy(HR, 0.715; 95%CI, 0.512-0.998; P=0.049). For details, please see also Table 2.
| Variables | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|
| HR (95%CI) | P | HR (95%CI) | P | |
| Treatment | ||||
| Surgery alone | 1.000 (Reference) | 1.000 (Reference) | ||
| Surgery + radiation | 0.670 (0.502~0.894) | 0.007 | 0.715 (0.512~0.998) | 0.049 |
| Age | ||||
| ≤60 y | 1.000 (Reference) | 1.000 (Reference) | ||
| >60 y | 1.130 (0.706~1.809) | 0.611 | 1.631 (1.038~2.564) | 0.034 |
| Sex | ||||
| Female | 1.000 (Reference) | 1.000 (Reference) | ||
| Male | 1.557 (1.025~2.367) | 0.038 | 1.371 (0.901 ~2.085) | 0.141 |
| Race | ||||
| White | 1.000 (Reference) | 1.000 (Reference) | ||
| Other | 1.054 (0.679~1.635) | 0.816 | 1.000 (0.623 ~1.605) | 0.999 |
| Laterality | ||||
| Left | 1.000 (Reference) | 1.000 (Reference) | ||
| Right | 0.843 (0.556~1.278) | 0.420 | 0.787 (0.512~1.210) | 0.276 |
| Tumor size | ||||
| ≤10 cm | 1.000 (Reference) | 1.000 (Reference) | ||
| >10 cm | 1.691 (1.069~2.676) | 0.025 | 1.326 (0.813~2.163) | 0.258 |
| Disease stage | ||||
| Localized | 1.000 (Reference) | 1.000 (Reference) | ||
| Regional | 1.625 (0.967 ~2.730) | 0.067 | 1.362 (0.777~2.386) | 0.281 |
| Distant | 3.045 (1.810~5.121) | <0.001 | 2.687 (1.616~4.466) | <0.001 |
| Grade | ||||
| I+II | 1.000 (Reference) | 1.000 (Reference) | ||
| III + IV | 2.456 (0.871~6.928) | 0.089 | 1.620 (0.531~4.942) | 0.397 |
| Unknown | 2.732 (1.062~7.031) | 0.037 | 2.462 (0.884~6.856) | 0.085 |
| Lymph node status | ||||
| Negative | 1.000 (Reference) | 1.000 (Reference) | ||
| Positive | 2.469 (1.148~5.314) | 0.021 | 3.165 (1.349~7.426) | 0.008 |
| Unknown | 0.864 (0.526~1.421) | 0.566 | 1.237 (0.729~2.100) | 0.430 |
| Chemotherapy | ||||
| No/Unknown | 1.000 (Reference) | 1.000 (Reference) | ||
| Yes | 1.233 (0.786~1.934) | 0.362 | 1.216 (0.764~1.934) | 0.410 |
HR: Hazard Ratio, CI: Confidence Interval
A
B
1.00-
Treatment+ Surgery Alone - Surgery+Radiation
1.00-
Treatment+ Surgery Alone + Surgery+Radiation
Overall Survival (%)
0.75-
Log rank P = 0.031
0.75
Log rank P = 0.698
HR (95%CI): 0.637 (0.419 - 0.968)
Overall Survival (%)
HR (95%CI): 0.861 (0.402 - 1.843)
0.50
0.50
0.25-
0.25
0.00
0.00
0
30
60
90
120
150
180
210
240
270
0
30
60
90
120
50
180
210
240
270
Survival Months
Survival Months
Number at risk
Number at risk
70
36
15
10
5
4
3
1
1
0
-
19
12
5
3
2
2
2
1
1
0
66
36
20
14
5
2
1
1
1
0
23
15
8
4
3
1
1
0
0
0
3.3 Exploratory analysis
Based on known high-risk features for relapse or death(advanced age, lymph node status positive, advanced disease stages, large tumor diameter, and histological differ- entiation poor), patients after PSM are stratified into two prognostic groups: low-risk group(n=42) included patients with ≤1 risk factor and the high-risk group(n=136) included those with ≥2 risk factors. The median OS of the low-risk group was 53.00 months (95%CI, 13.78-92.22 months), respectively, whereas the median OS of the high- risk group was 34.00 months (95%CI, 24.49-43.51 months)(P=0.316). In the high-risk group, the adjuvant postoperative radiotherapy was significantly associated with more prolonged survival(median OS: 46 vs. 33 months, P=0.031; Fig. 3A), but not the low-risk group(median OS: 53 vs. 40 months, P= 0.698; Fig. 3B).
4 Discussion
From 2000 to 2018, 636 patients were included in our study through the SEER database; after PSM, 178 patients were included for further survival analysis. The KM survival analysis and multivariate Cox regression analysis results showed that surgical treat- ment combined with radiotherapy to treat ACC improved OS compared to surgery alone significantly, and age, disease stage, lymph node status, and adjuvant radiotherapy were found to be independent factors influencing the overall survival of ACC patients who underwent radical adrenalectomy. Based on known high-risk features for high-risk groups, postoperative adjuvant radiotherapy has shown a survival benefit. In clinical practice, ACC patients who underwent radical adrenalectomy could be evaluated for the survival benefit of adjuvant radiotherapy by high-risk features for relapse or death.
Considering the highly aggressive behavior of ACC, the only chance for cure in patients without metastatic disease is complete primary tumor resection(R0) [12]. However, the guidelines did not reach a definitive consensus on adjuvant radiotherapy. Radiotherapy is only recommended in patients with R1 or Rx resection or stage III, not for routine use in patients with stage I-II and R0 resection [10]. This is consistent with our observed data: advanced disease patients are more likely to receive adjuvant radiotherapy. Since radio- therapy is infrequently recommended for adjuvant therapy in ACC patients who under- went radical adrenalectomy, the value of adjuvant radiotherapy in these patients has not been adequately elucidated. In this study, before PSM, it could be due to the high num- ber of patients who did not receive radiotherapy and the resultant selection bias, no sur- vival benefit from postoperative adjuvant radiotherapy in ACC patients who underwent radical adrenalectomy. It may also be the reason why the effectiveness of radiotherapy
in ACC patients undergoing surgical resection has not yet been proven. PSM is a good way to reduce selection bias by matching individuals with similar characteristics in the two groups, thus producing a more comparable study group and consequently leading to more comparable outcomes [13]. The SEER database contains large numbers of can- cer patients’ demographic, clinicopathological, treatment, and follow-up information, thus ensuring data representativeness [14]. Therefore, we used the SEER database for the study analyses and PSM to reduce selection bias and deeply explore adjuvant radio- therapy’s effectiveness in ACC patients who underwent radical adrenalectomy.
ACC was considered a radiotherapy-resistant tumor in previous studies [15]. The previous SEER database analysis found no direct link between radiotherapy and overall survival or cancer-specific survival(CSS) in ACC patients [16]. This might be because the study was meant to assess the efficacy of all ACC patients, including nonsurgical and metastatic ACC participants, so the value of radiotherapy in adjuvant therapy had not been well elucidated. Afterward, studies by Wu, Kan, and Ma, Shuqing et al., using the SEER database, observed that postoperative radiotherapy was associated with the survival of post-surgical patients; the role of radiotherapy was verified in postoperative ACC patients [17, 18]. Another study showed that adjuvant radiotherapy might improve the survival outcomes in ACC patients with positive surgical resection Margins; mean- while, the results of another PSM study further suggest that adjuvant radiotherapy was associated with a significant improvement in overall survival and relapse-free survival, regardless of surgical Margin status; regrettably, only 14.4% of the patients with com- plete resection received adjuvant radiotherapy in real-world [19, 20]. This observation is consistent with our findings that postoperative radiotherapy(14.94%) was not a routine adjuvant therapy. However, it was still unclear whether radiotherapy affects the long- term survival of ACC patients who underwent radical adrenalectomy in the above-men- tioned studies.
Radiotherapy may lead to serious side effects such as tissue damage and immune sys- tem disorder in the human body, and this may also be one of the reasons that many of the guidelines are against the routine use of radiotherapy in ACC patients [21]. Rapid advances in imaging and radiotherapy could be delivered at higher doses and more highly conformally, improving radiotherapy accuracy while mitigating side effects [22]. We review the developmental processes of treatment in ACC, finding that the role of radiotherapy is increasingly apparent. Previous radiotherapy was mainly used for the treatment of advanced ACC to alleviate pain because of metastases [23]. Later research found that adjuvant radiotherapy could reduce the postoperative recurrence rate and risk of death in ACC patients; however, they did not observe any statistical differences in overall survival [6, 19]. In an extensive study, after propensity matching analysis, adjuvant radiotherapy after gross resection of ACC was observed to improve RFS and OS [20]. Recently, the safety and efficacy of adjuvant radiotherapy were confirmed in localized ACC and advanced ACC patients, and the survival outcomes of ACC have improved significantly, while the side effects were also within the acceptable limit [9, 24]. Now, our study confirmed that adjuvant radiotherapy was also effective in ACC patients who underwent radical adrenalectomy, especially in those with multiple high-risk fea- tures for relapse or death. Therefore, it could be considered for selectively taking radio- therapy as one of the routine options for treating ACC.
Nevertheless, this study is subject to certain limitations. Firstly, the SEER database lacks comprehensive pathological immunohistochemical data and treatment details, including the expression of markers such as p53 and Ki-67, hormone secretion profiles, surgical margin status, disease recurrence, and specific chemotherapy and radiother- apy protocols. Recent research indicates that Ki-67 is significantly associated with the prognosis of various tumors, including ACC [25]. Furthermore, the database does not document detailed chemotherapy regimens, such as mitotane dosage and blood concen- tration, nor does it provide explanations for other chemotherapy protocols like etopo- side, cisplatin, doxorubicin, and mitotane (EDP-M), both of which are relevant to ACC prognosis [26, 27]. Secondly, the absence of information on radiotherapy dosage and fur- ther specifics, such as the timing of radiotherapy initiation post-surgery, may also influ- ence prognostic outcomes, thus compromising the study’s comprehensiveness. Thirdly, as a retrospective analysis, the study is inherently susceptible to selection bias and may be influenced by racial and regional variations. Consequently, these findings require vali- dation through prospective trials.
5 Conclusion
This study determined that patients with ACC undergoing radical adrenalectomy may experience benefits from postoperative adjuvant radiotherapy. Subsequent research indicates that individuals classified within high-risk groups are more likely to derive sur- vival advantages from adjuvant radiotherapy. However, this conclusion warrants further investigation for confirmation.
What does this study add to the clinical work? We found that ACC patients after radical adrenalectomy could benefit from adjuvant radiotherapy, especially in high-risk patients. So, we can take ACC patients after radical adrenalectomy and with more high- risk features(risk factor ≥2) as a potential beneficiary of adjuvant radiotherapy in clinical decisions.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1007/s12672-025-03653-2.
Supplementary material 1
Acknowledgements
We appreciate the SEER database for providing clinical data. And we sincerely thank our international colleagues for their invaluable assistance with language-related matters.
Author contributions
All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by [Minqin He] and [Minjuan He]. The first draft of the manuscript was written by [Minjuan He], and all authors commented on previous versions. All authors read and approved the final manuscript.
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Data availability
All raw data are available upon reasonable request.
Declarations
Ethics approval and consent to participate
The SEER is a publicly available database with anonymous patient data. So our hospital ethics committee exempted ethics approval.Not applicable.
Consent for publication
All authors agree to publish.
Competing interests
The authors declare no competing interests.
Received: 25 April 2025 / Accepted: 15 September 2025 Published online: 09 October 2025
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