1

Introduction

Adrenocortical carcinoma is a rare malignancy, with only approximately 600 incident cases diagnosed annually in the United States [ ]. Patients often have nonspecific symptoms and roughly a quarter of patients may present with advanced disease [ ]. Given this, patients with stage III and IV disease have reported 5-year overall survival rates of 24-50% and 0-17%, respectively [ ].

The American Joint Committee on Cancer (AJCC) has 2 definitions of stage III adrenocortical carcinoma: 1) lymph-node negative disease (T3-4N0M0) or 2) lymph-node positive disease (TanyN1M0). Patients with stage IV disease must have metastatic spread (TanyNanyM1) [ ]. Even among those with surgically resectable disease, 70% of patients may have a recurrence within 28 months, implying aggressive tumor biology [ ]. Characterizing which patients are at higher risk for poor oncologic outcomes may help define roles for adjuvant treatment, closer surveillance schedules, and clinical trial enrolment. Though a paucity of such literature exists, owing to the disease’s rarity, prior literature suggests that lymph node involvement portends a worse prognosis. Importantly, this represents an opportunity for more precise stratification within the AJCC staging system, to improve alignment of stage and tumor risk [ , , ].

In this study, we assessed survival outcomes in patients with clinical stage III lymph node negative, clinical stage III lymph node positive, and clinical stage IV disease. We hypothesize that patients with clinical stage III lymph node positive adrenocortical carcinoma will have inferior survival compared to those with clinical stage III lymph node negative disease. Instead, those patients with stage III node positive disease will exhibit survival patterns similar to patients with stage IV disease (i.e., those with metastasis). Consequently, we should consider an updated staging classification that differentiates between stage III lymph node positive and lymph node negative disease.

2

Methods

2.1

Study population and outcomes

The National Cancer Database (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC’s NCDB and the hospitals participating in the CoC’s NCDB are the source of de-identified data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions by the authors. There are over 1,500 accredited hospitals that are required to report new cancer diagnoses to the NCDB. The NCDB captures >70% of new cancer cases reported each year. Information regarding patient demographics, cancer staging, tumor characteristics, surgical treatment, and patient prognosis is recorded [ ].

From the NCDB we captured 4,311 patients with adrenocortical carcinoma from 2010 to 2017. We included only those with complete treatment and clinical staging data ( N = 1,781) ( Fig. 1 ). Only those with clinical stage III or IV disease were included ( N = 917). Only 109 patients with stage III or IV disease and complete pathologic data were found in the NCDB.

NCDB cohort construction for patients with AJCC stage III lymph negative, stage III lymph node positive, and stage IV clinical adrenocortical carcinoma.

Our primary outcome was overall survival. The primary exposure was presence of clinical lymph node positive disease in patients with stage III adrenocortical carcinoma. We adjusted multivariable models for age, receipt of surgery, receipt of systemic therapy and Charlson Comorbidity Index.

3

Results

Final analysis included 917 patients from 2010 to 2017, 322 (35.1%) patients with lymph node negative stage III disease, 67 (7.3%) patients with lymph node positive stage III disease, and 528 (57.6%) with stage IV disease. Demographic information for each cohort is described in Table 1 . Table 2 Median follow-up was 11.07 months (IQR 3.75-30.06). The mean age of the stage III lymph node positive group was 58.1 years (SD 15.2) compared to 54.0 (SD 17.5) and 54.2 (SD 16.4) for the stage III lymph node negative and stage IV groups, respectively. A greater percentage of patients with stage III lymph node negative (75.8%) disease received surgery, compared with stage III lymph node positive (58.2%), and stage IV (27.1%) disease. Similarly, patients deemed stage III lymph node negative (56.2), underwent systemic therapy more commonly than those with stage III node positive (43.3%) or stage IV (36.2%) disease.

Table 1

Demographics.

Demographics	cStage III LN (-)		cStage III LN (+)		cStage IV
Variable	Count	Percentage/SD	Count	Percentage/SD	Count	Percentage/SD
Total	322		67		528
Lymph node dissection *
LN dissected	81	25.2%	36	53.7%	72	13.6%
LN not dissected/unknown	241	74.8%	31	46.3%	456	86.4%
Tumor grade
1	8	2.5%	1	1.5%	9	1.7%
2	10	3.1%	2	3.0%	8	1.5%
3	38	11.8%	5	7.5%	56	10.6%
4	21	6.5%	1	1.5%	22	4.2%
Cell type undetermined	245	76.1%	58	86.6%	433	82.0%
Received surgery *
Yes	244	75.8%	39	58.2%	143	27.1%
No	78	24.2%	28	41.8%	385	72.9%
Systemic therapy *
Yes	181	56.2%	29	43.3%	191	36.2%
No	141	43.8%	38	56.7%	337	63.8%
Chemotherapy *
None	179	55.6%	29	43.3%	190	36.0%
Neoadjuvant	6	1.9%	2	3.0%	20	3.8%
Adjuvant	118	36.6%	23	34.3%	113	21.4%
Unknown/Unknown sequence	19	5.9%	13	19.4%	205	38.8%
Age, y	54.0	17.5	58.1	15.2	54.2	16.4
Sex
Female	183	56.8%	37	55.2%	322	61.0%
Male	139	43.2%	30	44.8%	206	39.0%
Race
White	267	82.9%	60	89.6%	445	84.3%
Black	42	13.0%	4	6.0%	58	11.0%
Native American	2	0.6%	1	1.5%	0	0.0%
Asian	7	2.2%	1	1.5%	11	2.1%
Other	4	1.2%	1	1.5%	14	2.7%
Charlson comorbidity index
0	233	72.4%	50	74.6%	389	73.7%
1	63	19.6%	9	13.4%	98	18.6%
2	17	5.3%	3	4.5%	28	5.3%
3	9	2.8%	5	7.5%	13	2.5%
Distance from treatment center, mi *
≤6.4	68	21.1%	14	20.9%	151	28.6%
>6.4–16.2	67	20.8%	20	29.9%	139	26.3%
>16.2–31	51	15.8%	12	17.9%	71	13.4%
>31	105	32.6%	14	20.9%	137	25.9%
N/A	31	9.6%	7	10.4%	30	5.7%
Annual income *
≥$63,333	85	26.4%	21	31.3%	188	35.6%
$50,354–$63,332	84	26.1%	20	29.9%	116	22.0%
$40,227–$50,353	70	21.7%	14	20.9%	87	16.5%
<$40,227	48	14.9%	5	7.5%	101	19.1%
N/A	35	10.9%	7	10.4%	36	6.8%
Regional education *
<6.3%	76	23.6%	12	17.9%	135	25.6%
6.3%–10.8%	70	21.7%	23	34.3%	135	25.6%
10.9%–17.5%	81	25.2%	8	11.9%	104	19.7%
≥17.6%	60	18.6%	17	25.4%	118	22.3%
N/A	35	10.9%	7	10.4%	36	6.8%
Insurance status
Private	171	53.1%	28	41.8%	256	48.5%
Not Insured	17	5.3%	5	7.5%	33	6.3%
Medicaid	29	9.0%	7	10.4%	59	11.2%
Medicare	83	25.8%	27	40.3%	153	29.0%
Other government	13	4.0%	0	0.0%	7	1.3%
Insurance status unknown	9	2.8%	0	0.0%	20	3.8%
Hospital type
Academic/Research program	156	48.4%	31	46.3%	216	40.9%
Community cancer program	7	2.2%	3	4.5%	22	4.2%
Comprehensive community cancer program	55	17.1%	13	19.4%	129	24.4%
Integrated network cancer program	42	13.0%	10	14.9%	62	11.7%
N/A	62	19.3%	10	14.9%	99	18.8%

Only gold members can continue reading. Log In or Register to continue

Related posts:

Tumor involvement of the trigone and urethra at the time of robot-assisted radical cystectomy is associated with adverse oncological outcomes Understanding the microbiome as a mediator of bladder cancer progression and therapeutic response 5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data The use of nephron-sparing intervention does not appear to be compromised after a period of active surveillance for patients with cT1 renal masses Causal relationship between bladder cancer and gut microbiota contributes to the gut-bladder axis: A two-sample Mendelian randomization study Clinical significance of PSA dynamics in castration-sensitive prostate cancer treated with ARSI doublet therapy: A multicenter study

Stay updated, free articles. Join our Telegram channel

Join