Check for updates
DOI: 10.1002/jso.27161
Contemporary conditional cancer-specific survival rates in surgically treated adrenocortical carcinoma patients: A stage-specific analysis
Andrea Panunzio MD1,2 İD Francesco Barletta2,3 | | Stefano Tappero 2,4,5 Cristina Cano Garcia2,6 | Mattia Piccinelli2,7 | Reha-Baris Incesu2,8 |
Kyle W. Law2 Zhe Tian2 2 Alessandro Tafuri1 Derya Tilki 8,9,10 Ottavio De Cobelli7 | Felix K. H. Chun6 | Carlo Terrone 4,5 Alberto Briganti3 |
Fred Saad2 Shahrokh F. Shariat 11,12,13,14 |
|
Isabelle Bourdeau1 15
|
Maria A. Cerruto1 | Alessandro Antonelli1 | Pierre I. Karakiewicz2
1Department of Urology, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Verona, Italy
2Division of Urology, Cancer Prognostics and Health Outcomes Unit, University of Montréal Health Center, Montréal, Québec, Canada
3Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
4Department of Surgical and Diagnostic Integrated Sciences (DISC), University of Genova, Genova, Italy
5Department of Urology, IRCCS Policlinico San Martino, Genova, Italy
‘Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany
7Department of Urology, IEO European Institute of Oncology, IRCCS, Milan, Italy 8Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
9 Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
10Department of Urology, Koc University Hospital, Istanbul, Turkey
11Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
12Departments of Urology, Weill Cornell Medical College, New York, New York, USA
13Department of Urology, University of Texas Southwestern, Dallas, Texas, USA
14Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan
15Department of Medicine and Research Center, Division of Endocrinology, Centre hospitalier de l’Université de Montreal (CHUM), Montreal, Canada
Correspondence
Andrea Panunzio, MD, Department of Urology, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy. Email: panunzioandrea@virgilio.it
Abstract
Background and Objectives: We examined the effect of disease-free interval (DFI) duration on cancer-specific mortality (CSM)-free survival, otherwise known as the effect of conditional survival, in surgically treated adrenocortical carcinoma (ACC) patients. Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2018), 867 ACC patients treated with adrenalectomy were identified. Conditional survival estimates at 5-years were assessed based on DFI duration and according to stage at presentation. Separate Cox regression models were fitted at baseline and according to DFI.
Results: Overall, 406 (47%), 285 (33%), and 176 (20%) patients were stage I-II, III and IV, respectively. In conditional survival analysis, providing a DFI of 24 months,
5-year CSM-free survival at initial diagnosis increased from 66% to 80% in stage I-II, from 35% to 66% in stage III, and from 14% to 36% in stage IV. In multivariable Cox regression models, stage III (hazard ratio [HR]: 2.38; p < 0.001) and IV (HR: 4.67; p < 0.001) independently predicted higher CSM, relative to stage I-II. The magnitude of this effect decreased over time, providing increasing DFI duration. Conclusions: In surgically treated ACC, survival probabilities increase with longer DFI duration. This improvement is more pronounced in stage III, followed by stages IV and I-II patients, in that order. Survival estimates accounting for DFI may prove valuable in patients counseling.
KEYWORDS ACC, adrenalectomy, conditional survival
1 INTRODUCTION |
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy accounting for 0.2% of all cancer deaths in the United States.1,2 In patients with localized or even locally advanced disease, complete surgical resection provides the only mean of cure.3 However, most ACC patients present at advanced stage at initial diagnosis.4,5 In these patients surgical management, if feasible, is recommended by international guidelines, in addition to systemic therapy.3 In conse- quence, survival estimates for surgically treated ACC patients may show important differences according to stage distribution. Indeed, two previous single-institution (n = 346 and n = 1527), two multi- institutional (n = 1268 and n = 389), as well as two population-based (n = 32010 and n = 36711) studies demonstrated important differ- ences, where 5-year cancer-specific mortality (CSM)-free survival rates ranged from 40% to 70% in localized ACC, from 15% to 40% in locally advanced ACC, and from to 10% to 25% in metastatic ACC. However, these figures are based on small numbers of observations. Moreover, they are derived from conventional survival analyses that do not account for disease-free interval (DFI) duration. It is of note that the risk of death due to cancer at initial cancer diagnosis is usually highest. However, the hazard function usually decreases in proportion to duration of event-free follow-up. According to reports that addressed primaries other than ACC, some investigators indeed demonstrated that prognosis after initial cancer diagnosis and subsequent treatment improved with longer DFI duration.12-16 This effect, known as conditional survival, has been tested in bladder,12 kidney,13 upper urinary tract,16 as well as in other non-urological malignancies.14,15 Based on these data, conditional survival that accounted for DFI is a better suited prognosticator of long-term cancer control outcomes than survival predicted at initial diagnosis.
To date contemporary, large-scale, and stage-specific analyses addressing CSM-free survival rates at baseline, as well as according to DFI duration have not been completed in surgically treated ACC patients. We addressed this knowledge gap within a large population- based data repository. We hypothesized that CSM-free survival rates
in surgically treated ACC patients may be derived from much larger patients subgroups than in previous publications.6-11 We also postulated that, as in other primaries, stage-specific CSM-free survival rates improve with longer DFI duration. All analyses relied on Surveillance, Epidemiology, and End Results (SEER17) database (2004-2018).
2 MATERIALS AND METHODS |
2.1 Study population and outcome of interest |
The SEER database samples 48% of the United States and approximates the United States in terms of its demographic composition, as well as its cancer incidence.17 Within the SEER database (2004-2018), we focused on patients 18 years older with histologically confirmed ACC (International Classification of Disease for Oncology [ICD-O-3] site code C74.0/C74.9; histologic code: “8370/3: Adrenal cortical carcinoma,” “8010/3: Carcinoma, NOS,” and “8140/3: Adenocarcinoma, NOS”), who underwent adrenalectomy as primary treatment (n = 929). Exclusion criteria consisted of patients with unknown TNM stage (n = 53), according to European Network for the Study of Adrenal Tumors (ENSAT),3 as well as with unknown vital status (n = 9). These selection criteria yielded 867 surgically treated ACC patients assessable for the analyses. CSM (death due to ACC) represented the endpoint of interest and was defined according to SEER mortality code.
2.2 Statistical analyses |
Descriptive statistics included frequencies and proportions for categorical variables. Medians and interquartile ranges (IQR) were reported for continuously coded variables. The study analyses relied on three steps. First, 5-year CSM-free survival estimates at initial diagnosis were derived from Kaplan-Meier (KM) plots according to
three specific ENSAT stage groupings: I-II, III, and IV. Second, conditional survival analyses computed CSM-free survival rates at 5 years, according to DFI duration of 6, 12, 18, and 24 months, within each ENSAT stage grouping. According to previous methodology,15 conditional survival was calculated as the probability of surviving forx additional years, given a DFI of y months. Finally, separate multivariable Cox regression models addressing CSM were fitted, at baseline and according to specific DFI duration (6, 12, 18, and 24 months). Covariates consisted of age at diagnosis, primary tumor size, tumor grade and postoperative systemic therapy status (not received vs. received). The change in the magnitude of ENSAT stage groupings III and IV in predicting higher mortality rates over time relative to stage I-II, was graphically displayed. All tests were two- sided with a level of significance set at p < 0.05. R software environment for statistical computing and graphics (version 4.1.2; R foundation for Statistical Computing18) was used for all analyses.
3 RESULTS |
3.1 Descriptive characteristics of the study population |
In the entire cohort of 867 surgically treated ACC patients, median age was 56 years (IQR 44-65, Table 1). Overall, 533 (61%) patients were female, most were Caucasians (n = 615, 71%) and were identified in the West (n = 435, 51%). Median primary tumor size was 10.5 cm (IQR 7.5-14.5). According to ENSAT stage, the overall ACC population was distributed as follows: 406 (47%) stage I-II versus 285 (33%) stage III versus 176 (20%) stage IV. Systemic therapy was administered postoperatively in 359 (41%) cases. Specifically, 119 of 406 (29%) received systemic therapy in stage I-II, 130 of 285 (46%) received systemic therapy in stage III, and 110 of 176 (63%) received systemic therapy in stage IV.
3.2 Conditional survival analysis according to ENSAT stage groupings |
Conditional survival methodology was sequentially applied to each of three specific ENSAT stage groupings, namely: I-II, III and IV (Figure 1, Table 2). In 406 ENSAT stage I-II patients, 5-year CSM- free survival at initial diagnosis was 66%. Provided a DFI duration of 6 months, CSM-free survival estimate at 5 years was 67%. Provided a DFI duration of 12, 18, and 24 months, CSM-free survival estimates at 5 years were 70%, 74%, and 80%, respectively. After DFI duration of 6, 12, 18, and 24 months, respectively 370 (91%), 332 (82%), 303 (75%), and 272 (67%) patients were assessable, compared to baseline.
In 285 ENSAT stage III patients, 5-year CSM-free survival at initial diagnosis was 35%. Provided a DFI duration of 6 months, CSM- free survival estimate at 5 years was 40%. Provided a DFI duration of 12, 18, and 24 months, CSM-free survival estimates at 5 years were 47%, 55%, and 66%, respectively. After DFI duration of 6, 12, 18, and
| Variables | Overall (n = 867) |
|---|---|
| Age at diagnosis (years) | 56 (44-65) |
| Sex | |
| Male | 334 (39) |
| Female | 533 (61) |
| Marital status | |
| Married | 522 (60) |
| Unmarried | 320 (37) |
| Unknown | 25 (3) |
| Race/ethnicity | |
| Caucasian | 615 (71) |
| Hispanic | 112 (13) |
| African American | 82 (9) |
| Asian | 53 (6) |
| Others/unknown | 5 (1) |
| Geographic region | |
| West | 435 (51) |
| South | 212 (24) |
| North-East | 139 (16) |
| Midwest | 81 (9) |
| Primary tumor size (cm) | 10.5 (7.5-14.5) |
| Tumor grade | |
| G1-2 | 85 (10) |
| G3-4 | 156 (18) |
| GX | 626 (72) |
| ENSAT stage | |
| Stage I | 50 (6) |
| Stage II | 356 (41) |
| Stage III | 285 (33) |
| Stage IV | 176 (20) |
| Systemic therapy | |
| Not received | 508 (59) |
| Received | 359 (41) |
Abbreviation: ENSAT, European Network for the Study of the Adrenal Tumors.
24 months, respectively 232 (81%), 181 (64%), 145 (51%), and 113 (40%) patients were assessable, compared to baseline.
In 176 ENSAT stage IV patients, 5-year CSM-free survival at initial diagnosis was 14%. Provided a DFI duration of 6 months, CSM- free survival estimate at 5 years was 19%. Provided a DFI duration of
WILEY
(A)
Conditional Survival in stage I-II
(B)
Conditional Survival in stage III
1.0
1.0
Survival Probability
0.8
Survival Probability
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0.0
0.0
0
6
12
18
24
30
36
42
48
54
60
0
6
12
18
24
30
36
42
48
54
60
Months survived after adrenalectomy
Months survived after adrenalectomy
(C)
Conditional Survival in stage IV
1.0
Survival Probability
0.8
0.6
0.4
0.2
0.0
0
6
12
18
24
30
36
42
48
54
60
Months survived after adrenalectomy
| Disease-free interval | 0 | 6 | 12 | 18 | 24 |
| STAGE I-II | |||||
| Nº at riskª | 406 | 370 (91%) | 332 (82%) | 303 (75%) | 272 (67%) |
| Nº of eventsb | 110 | 100 | 86 | 69 | 49 |
| 5-year CSM free survival | 66%c | 67% | 70% | 74% | 80% |
| STAGE III | |||||
| Nº at riskª | 285 | 232 (81%) | 181 (64%) | 145 (51%) | 113 (40%) |
| Nº of eventsb | 146 | 115 | 80 | 55 | 33 |
| 5-year CSM free survival | 35%c | 40% | 47% | 55% | 66% |
| STAGE IV | |||||
| Nº at riskª | 176 | 131 (74%) | 88 (50%) | 63 (36%) | 50 (28%) |
| Nº of eventsb | 123 | 77 | 51 | 35 | 28 |
| 5-year CSM free survival | 14%c | 19% | 24% | 32% | 36% |
ªAt the beginning of the interval;
bAt the end of the interval;
“Kaplan-Meier derived estimated 5-years CSM free survival at diagnosis.
12, 18, and 24 months, CSM-free survival estimates at 5 years were 24%, 32%, and 36%, respectively. After DFI duration of 6, 12, 18, and 24 months, respectively 131 (74%), 88 (50%), 63 (36%), and 50 (28%) patients were assessable, compared to baseline.
3.3 Multivariable Cox regression models predicting CSM |
In multivariable Cox regression models predicting CSM at baseline, ENSAT stage III (Hazard Ratio [HR]: 2.38, 95% confidence interval [CI]: 1.87-3.03; p < 0.001), and ENSAT stage IV (HR: 4.67, 95% CI: 3.54-6.16, p < 0.001) were independent predictors of higher CSM, relative to ENSAT stage I-II, after adjustment for all covariates (Table 3). In multivariable Cox regression models addressing CSM, providing DFI duration of 6 versus 12 versus 18 versus 24 months, ENSAT stage III (HR: 2.22-1.49) and IV (HR: 3.75-3.01) invariably represented independent predictors (p < 0.05 in all cases; Table 3, Figure 2).
4 DISCUSSION |
In many primaries it has been previously reported that after treatment, prognosis improved according to increased DFI duration.12-16 This effect, known as conditional survival, is important because it could provide clinicians more accurate patients survival estimates, allowing individual counseling and personalized follow-up planning. Moreover, it could provide more encouraging survival estimates to patients with longer DFI. Two historical studies previously addressed DFI duration and the conditional survival concept in nonmetastatic surgically treated ACC patients, within a multi-institutional (1993-2014),19 and a population-based (1988-2012)20 database, respectively. However, both studies were affected by critical flaws that undermined their observations and conclusions. For example, Kim et al.19 addressed 3-year conditional survival rates in non-metastatic surgically treated ACC patients based on DFI duration of 24 months or more. Despite a large sample size at baseline (n = 192), important attrition due to mortality occurred and resulted in only 42 observations at a DFI of 36 months, based on which the subsequent conditional survival estimates were computed. Conversely, Xiao et al.2º relied on a large patient population (n = 641), to address conditional survival in surgically treated ENSAT stage I-III ACC patients. Unfortunately, their analyses relied on overall mortality as endpoint of interest. The latter is invariably critically contaminated by other-cause mortality (OCM). This contamination is particularly strong and rate-limiting in stages I, II, and III. In consequence, the two available reports addressing conditional survival in ACC do not provide sufficiently robust results to derive valid conclusions.
We addressed the two above limitations within a very large population-based data repository that allows the distinction between CSM and OCM, and that also significantly exceeded the sample size of Kim et al.19 study, even after accounting for attrition due to
| p Value | ‐ | 0.046 | <0.001 | |||
|---|---|---|---|---|---|---|
| (1.87-4.83) | ||||||
| CI) | (1.01-2.21) | |||||
| (95% | ||||||
| 24 | HR | Ref. | 1.49 | 3.01 | ||
| p Value | ‐ | 0.002 | <0.001 | |||
| CI) | (1.23-2.35) | (1.59-3.66) | ||||
| (95% | ||||||
| 18 | HR | Ref. | 1.70 | 2.41 | ||
| Value | <0.001 | <0.001 | ||||
| p | ‐ | |||||
| CI) | (1.37-2.45) | (2.11-4.27) | ||||
| (95% | ||||||
| HR | Ref. | 1.83 | 2.99 | |||
| 12 | ||||||
| <0.001 | ||||||
| Value | <0.001 | |||||
| p | ‐ | |||||
| CI) | (1.72-2.88) | (2.76-5.10) | ||||
| (95% | ||||||
| 6 | 3.75 | |||||
| HR | Ref. | 2.22 | ||||
| Value | <0.001 | |||||
| p | ‐ | <0.001 | ||||
| CI) | (1.87-3.03) | (3.53-6.13) | ||||
| (95% | ||||||
| 0 | HR | Ref. | 2.38 | 4.65 | ||
| stage | ||||||
| (months) | I-II | III | IV | |||
| DFI | ENSAT | Stage | Stage | Stage | ||
PANUNZIO ET AL. 18 and 24 months Note: Models adjusted for age at diagnosis, primary tumor size, tumor grade, and systemic therapy status. Abbreviations: CI, confidence interval; HR, hazard ratio. TABLE 3 Multivariable Cox regression models predicting cancer-specific mortality in 867 surgically treated adrenocortical carcinoma patients, providing a disease-free interval (DFI) of 6, 12, 10969098, 2023, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jso.27161 by National Library Of Medicine, Wiley Online Library on [03/04/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
6
Hazard Ratio
4
stage IV
2
stage III
stage I-II (Ref.)
0
0
6
12
18
24
Months survived
mortality during follow-up. Relying on SEER, we hypothesized that CSM-free survival rates in surgically treated ACC patients may be derived from much larger patients subgroups than in previous publications,6-11 and that, as in other primaries, stage-specific CSM-free survival rates improve with longer DFI duration. We made the following observations.
First, despite the extremely large size of the SEER database that represents the 48% sample of the US population, we only identified 867 surgically treated ACC patients. This number is fourfold higher than the number of patients included in the multi-institutional study (n = 192),19 and higher than that of the historical population-based one (n = 641).2º Nonetheless, our patient population of surgically treated ACC attest to its rare entity status. Due to its larger sample size, the current analysis provides more generalizable observations than the two previous studies,19,20 in addition to be more contemporary.
Second, to address the effect of DFI duration on survival in surgically treated ACC patients, we relied on three specific ENSAT stage groupings namely: I-II, III and IV. Here, we respectively identified 406, 285, and 176 patients. In univariable KM analyses, 5-year CSM-free survival estimates computed at baseline, where DFI was equal to 0, were 66%, 35%, and 14% in respectively ENSAT stage I-II, III, and IV (p <0.001). In multivariable Cox regression models, ENSAT stage III and IV independently predicted higher CSM
at baseline, relative to ENSAT stage I-II. Taken together, these findings attest to the ability of ENSAT stage system to stratify CSM-free survival rates within surgically treated ACC patients, as according to international guidelines recommendations.
Third, in conditional survival analyses we recorded improved CSM-free survival rates according to DFI duration. Specifically, providing a 24-months DFI, 5-years CSM-free survival estimates at baseline improved from 66% to 80% in ENSAT stage I-II (4 = +14%), from 35% to 66% in ENSAT stage III (4 = +31%), and from 14% to 36% in ENSAT stage IV (4 = +22%), Taken together, our observations indicate that as in other primaries, longer DFI duration is associated with lower CSM. This relationship applied to all three ENSAT stage groupings, but its effect is more pronounced in stage III, followed by stage IV and I-II in that order. Additionally, these observations validate the concept of conditional survival, even in the lowest ACC ENSAT stages, where this effect was expected to be weakest, based on data from other primaries, such as renal cell carcinoma,13 and urothelial bladder cancer.12 In these primaries patients with most favorable tumor stages do not benefit from a decreasing CSM even after a lengthy DFI, based on virtually nonexistent risk of mortality. It is also noteworthy that the conditional survival phenomenon applies very strongly to metastatic ACC. This concept was not examined in the two previous historical and smaller sample size studies that tested the effect of DFI duration on conditional survival in ACC.19,20
Moreover, the observations made in metastatic surgically treated ACC patients within the current study are in agreement with other analyses that for example addressed metastatic renal cell carcinoma patients treated with radical nephrectomy,21 or various first line systemic therapies. 22,23
Finally, we tested the independent predictor status of ENSAT stages at all examined DFI timepoints (6, 12, 18, and 24 months). At all timepoints ENSAT stages III and IV represented independent predictors of higher CSM, relative to ENSAT stage I-II. Taken together, this observation indicates that the importance of ENSAT staging is maintained overtime, despite sample size attrition that applied to all ENSAT stage groupings in proportion to DFI duration. To the best of our knowledge, we are the first to validate ENSAT staging system in this fashion. Additionally, it is of interest to note that the hazard function associated with each ENSAT stage decreased with increasing DFI duration. In ENSAT stage III the most pronounced decreased is recorded between 6 and 12 months. Conversely, in ENSAT stage IV the most pronounced decreased is recorded between 0 and 6 months.
Despite its strength, the current study is not devoid of limitations. First, despite the large scale of SEER database, a suboptimal low number of individuals were identified. In conse- quence, stratified analyses addressing DFI timepoints of duration beyond 24 months could not be addressed. This observation is of importance, when the current study is compared to the two previous historical and smaller case reports, where lower number of observa- tions at baseline were included, but CSM-free survival was computed based on DFI durations as long as 36 months, which could not be achieved in the current study based on limited robustness of findings beyond DFI duration of 24 months. Second, our findings are based on vital status. Specifically, CSM represented the outcome of interest. Alternative analyses might rely on recurrence-free survival or metastatic progression that could provide a different but equally meaningful perspective in patient counseling, surveillance protocols, and treatment decision making. Unfortunately, the SEER database does not allow such analyses, due to absence of data pertaining these two endpoints. Third, SEER database does not provide information on potential prognostic factors other than ENSAT stage, such as mitotic index, venous invasion, surgical margins status and endocrine tumor activity,3 that could have allowed a better stratification of patients cohort into more specific prognostic groups. Additionally, a more detailed distinction between ENSAT stage I and II was not possible, due to sample size limitations that especially pertain to stage I. Therefore, ENSAT stage I and II were combined. However, this methodology was shared with previous ACC analyses that relied on SEER.5,24 Fourth, limited detail regarding treatment type was available. Specifically, the SEER database does provide information on adrenalectomy. However, it does not provide additional informa- tion on potential cytoreduction in more advanced disease stages. Similarly, systemic therapy status is provided. However, the type, dose, and duration of its administration are not provided. Fifth, the SEER database does not provide baseline patient comorbidities.
However, this limitation is accounted for by use of OCM that represent the ultimate endpoint of most clinically meaningful comorbidities. Specifically, OCM rates within the current study were 9.4%, 10.6%, and 7.7% in respectively ENSAT stage I-II, III, and IV. Therefore, it could be postulated that a not clinically meaningful proportion of ACC patients succumbed due to OCM, especially in lower disease stage, without affecting conditional survival. These as other limitations related to retrospective nature of the SEER, with potentially high selection bias apply to the current study, as well as to other analyses based on similar large-scale database.
5 CONCLUSIONS |
In surgically treated ACC patients, longer DFI duration is associated with increased survival probabilities. This improvement is more pronounced in ENSAT stage III, followed by ENSAT stage IV and ENSAT stage I-II patients, in that order. These observations provide more specific survival estimates to clinicians and are crucial for counseling of individual patients, who may be reassured that after each additional DFI time interval their likelihood of remaining disease-free increases.
AUTHOR CONTRIBUTIONS
Andrea Panunzio: conceptualization, methodology, formal analysis, writing original draft, writing review and editing, and visualization. Francesco Barletta: writing review and editing and visualization. Stefano Tappero: writing review and editing and visualization. Cristina Cano Garcia: writing review and editing and visualization. Mattia Piccinelli: writ- ing review and editing and visualization. Reha-Baris Incesu: writing review and editing and visualization. Zhe Tian: methodology, software, validation, formal analysis, and resources. Alessandro Tafuri: writing review and editing and visualization. Derya Tilki: writing review and editing and supervision. Ottavio De Cobelli: writing review and editing and supervision. Felix K. H. Chun: writing review and editing and supervision. Carlo Terrone: writing review and editing and supervision. Alberto Briganti: writing review and editing and supervision. Fred Saad: writing review and editing and supervision. Shahrokh F. Shariat: writing review and editing and supervision. Isabelle Bourdeau: writing review and editing and supervision. Maria A. Cerruto: writing review and editing and supervision. Alessandro Antonelli: writing review and editing and supervision. Pierre I. Karakiewicz: writing review and editing, supervision, project administration, and conceptualization. All authors contributed to the article and approved the submitted version.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
DATA AVAILABILITY STATEMENT
All data generated for this analysis were from the SEER database. The code for the analyses will be made available upon request.
ETHICS STATEMENT
All analyses and their reporting followed the SEER reporting guidelines. Due to the anonymously coded design of the SEER database, study-specific Institutional Review Board ethics approval was not required.
ORCID
Andrea Panunzio D https://orcid.org/0000-0002-9756-4632
REFERENCES
1. Else T, Kim AC, Sabolch A, et al. Adrenocortical carcinoma. Endocr Rev. 2014;35(2):282-326.
2. Bourdeau I, Mackenzie-Feder J, Lacroix A. Recent advances in adrenocortical carcinoma in adults. Curr Opin Endocrinol Diabetes Obes. 2013;20(3):192-197.
3. Fassnacht M, Dekkers OM, Else T, et al. European society of endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the european network for the study of adrenal tumors. Eur J Endocrinol. 2018;179(4):G1-G46.
4. Abdel-Rahman O. Revisiting the AJCC staging system of adrenocor- tical carcinoma. J Endocrinol Invest. 2022;45(1):89-94.
5. Wang S, Chen SS, Gao WC, et al. Prognostic factors of adrenocorti- cal carcinoma: an analysis of the surveillance epidemiology and end results (SEER) database. Asian Pac J Cancer Prev. 2017;18(10): 2817-2823.
6. Donatini G, Caiazzo R, do Cao C, et al. Long-term survival after adrenalectomy for stage I/II adrenocortical carcinoma (ACC): a retrospective comparative cohort study of laparoscopic versus open approach. Ann Surg Oncol. 2014;21(1):284-291.
7. Brix D, Allolio B, Fenske W, et al. Laparoscopic versus open adrenalectomy for adrenocortical carcinoma: surgical and oncologic outcome in 152 patients. Eur Urol. 2010;58(4):609-615.
8. Lombardi CP, Raffaelli M, de Crea C, et al. Open versus endoscopic adrenalectomy in the treatment of localized (stage I/II) adrenocorti- cal carcinoma: results of a multiinstitutional Italian survey. Surgery. 2012;152(6):1158-1164.
9. Mihai R, Iacobone M, Makay O, et al. Outcome of operation in patients with adrenocortical cancer invading the inferior vena cava — a european society of endocrine surgeons (ESES) survey. Langenbecks Arch Surg. 2012;397(2):225-231.
10. Tran TB, Liou D, Menon VG, Nissen NN. Surgical management of advanced adrenocortical carcinoma: a 21-year population-based analysis. Am Surg. 2013;79(10):1115-1118.
11. Livhits M, Li N, Yeh MW, Harari A. Surgery is associated with improved survival for adrenocortical cancer, even in metastatic disease. Surgery. 2014;156(6):1531-1541; discussion 1540-1.
12. Palumbo C, Mistretta FA, Knipper S, et al. How cancer-specific mortality changes over time after radical cystectomy: conditional survival of patients with nonmetastatic urothelial carcinoma of the urinary bladder. Urol Oncol. 2019;37(12):893-899.
13. Palumbo C, Mistretta FA, Knipper S, et al. Conditional survival of patients with nonmetastatic renal cell carcinoma: how Cancer- Specific mortality changes after nephrectomy. J Natl Compr Canc Netw. 2020;18(1):44-51.
14. Qaderi SM, Dickman PW, de Wilt JHW, Verhoeven RHA. Condi- tional survival and cure of patients with colon or rectal cancer: a population-based study. J Natl Compr Canc Netw. 2020;18(9): 1230-1237.
15. Skuladottir H, Olsen JH. Conditional survival of patients with the four major histologic subgroups of lung cancer in Denmark. J Clin Oncol. 2003;21(16):3035-3040.
16. Rosiello G, Palumbo C, Knipper S, et al. Contemporary conditional cancer-specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract. J Surg Oncol. 2020;121(7):1154-1161.
17. 7. About the SEER Program. SEER. Accessed September 5, 2022. https://seer.cancer.gov/about/overview.html
18. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing; 2020. https://www.R- project.org/
19. Kim Y, Margonis GA, Prescott JD, et al. Curative surgical resection of adrenocortical carcinoma: determining long-term outcome based on conditional disease-free probability. Ann Surg. 2017;265(1):197-204.
20. Xiao W, Zhu Y, Dai B, et al. Conditional survival among patients with adrenal cortical carcinoma determined using a national population- based surveillance, epidemiology, and end results registry. Oncotarget. 2015;6(42):44955-44962.
21. Bianchi M, Becker A, Hansen J, et al. Conditional survival after nephrectomy for renal cell carcinoma (RCC): changes in future survival probability over time: conditional survival after nephrec- tomy for RCC. BJU Int. 2013;111(8):E283-E289.
22. Motzer RJ, McDermott DF, Escudier B, et al. Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer. 2022;128(11):2085-2097.
23. Harshman LC, Xie W, Bjarnason GA, et al. Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF- targeted therapy: a population-based study. Lancet Oncol. 2012;13(9):927-935.
24. Thomas JJ, Tward JD. Stage presentation, care patterns, treatment outcomes, and impact of radiotherapy on overall survival for adrenocortical carcinoma. Clin Genitourin Cancer. 2021;19(5): 417-424.
How to cite this article: Panunzio A, Barletta F, Tappero S, et al. Contemporary conditional cancer-specific survival rates in surgically treated adrenocortical carcinoma patients: a stage-specific analysis. J Surg Oncol. 2023;127:560-567. doi:10.1002/jso.27161