Quantifying the rate and predictors of occult lymph node involvement in patients with clinically node-negative non-small cell lung cancer

Figures & data

Table 1. Characteristics of the patient population.

Parameter	All patients (N = 109,964)
Age (years)
<65	35653 (32.4%)
65–74	45205 (41.1%)
>74	29106 (26.5%)
Gender
Male	53817 (48.9%)
Female	56147 (51.1%)
Race
White	97850 (89.0%)
Black	8756 (8.0%)
Other	3358 (3.1%)
Comorbidity score
0	53395 (48.6%)
1	39661 (36.1%)
2	13014 (11.8%)
≥3	3895 (3.5%)
Facility type
Academic	36234 (33.0%)
Non-academic	73479 (66.8%)
Not recorded	251 (0.2%)
Histology
Adenocarcinoma	65953 (60.0%)
Squamous cell carcinoma	44011 (40.0%)
Clinical T stage
1	68700 (62.5%)
2	33356 (30.3%)
3	5979 (5.4%)
4	1929 (1.8%)
Tumor grade
Well differentiated	13236 (12.0%)
Moderately differentiated	53691 (48.8%)
Poorly differentiated	39094 (35.6%)
Not recorded	3943 (3.6%)
Tumor size
Median (interquartile range) (cm)	2.5 (1.7–3.6)
≤1 cm	7079 (6.4%)
1.1–2 cm	36284 (33.0%)
2.1–3 cm	29334 (26.7%)
3.1–4 cm	16525 (15.0%)
4.1–5 cm	8748 (8.0%)
5.1–6 cm	5240 (4.8%)
6.1–7 cm	2793 (2.5%)
> 7 cm	3961 (3.6%)
Surgery
Sublobar	16735 (15.2%)
Lobectomy	89460 (81.4%)
Pneumonectomy	3769 (3.4%)
Number of nodes removed
Median (interquartile range)	8 (5–14)
1–5	34753 (31.6%)
6–10	32999 (30.0%)
>10	34972 (31.8%)
Not reported	7240 (6.6%)
Days from diagnosis to surgery
Median (interquartile range)	29 (3–51)
0–30	56005 (50.9%)
31–60	33430 (30.4%)
61–90	12236 (11.1%)
>90	7407 (6.7%)
Not reported	886 (0.8%)

Table 2. Proportion of patients with occult pathologic nodal disease as stratified by tumor size and number of lymph nodes resected.

Tumor size	All patients		1–5 LNs resected		6–10 LNs resected		>10 LNs resected
	pN + Patients/Total patients	Occult LN positivity rate (%)	pN+ patients/Total patients	Occult LN positivity rate (%)	pN+ patients/Total patients	Occult LN positivity rate (%)	pN+ patients/Total patients	Occult LN positivity rate (%)
≤1.0 cm	308/7079	4.4	81/2980	2.7	95/1969	4.8	109/1665	6.6
1.1–2.0 cm	2810/36284	7.7	652/13535	4.8	888/10936	8.1	1096/9539	11.5
2.1–3.0 cm	3769/29334	12.8	752/9320	8.1	1176/9050	13.0	1590/9045	17.6
3.1–4.0 cm	2973/16525	18.0	475/4594	10.3	823/4986	16.5	1482/5856	25.3
4.1–5.0 cm	1768/8748	20.2	254/2057	12.3	483/2652	18.2	909/3387	26.8
5.1–6.0 cm	1180/5240	22.5	123/1086	11.3	305/1506	20.3	677/2282	29.7
6.1–7.0 cm	681/2793	24.4	65/500	13.0	164/806	20.3	397/1294	30.7
>7.0 cm	1046/3961	26.4	110/681	16.2	241/1093	22.0	602/1904	31.6
Total	14535/109964	13.2	2512/32241	7.8	4175/32998	12.7	6862/34972	19.6

LN: lymph node; pN+: pathologically node-positive.

Table 3. Proportion of patients with occult pathologic nodal disease as stratified by tumor size and surgical approach.

Tumor size	Sublobar resection		Lobectomy		Pneumonectomy
	pN+ patients/Total patients	Occult LN positivity rate (%)	pN+ patients/Total patients	Occult LN positivity rate (%)	pN+ patients/Total patients	Occult LN positivity rate (%)
≤ 1.0 cm	77/2369	3.3	219/4639	4.7	12/61	19.7
1.1–2.0 cm	345/7980	4.3	2400/27992	8.6	65/312	20.8
2.1–3.0 cm	266/3970	6.7	3293/24869	13.2	210/495	42.4
3.1–4.0 cm	132/1449	9.1	2475/14409	17.2	366/667	54.9
4.1–5.0 cm	60/526	11.4	1398/7624	18.3	310/598	51.8
5.1–6.0 cm	23/225	10.2	899/4488	20.0	258/527	49.0
6.1–7.0 cm	7/98	7.1	517/2342	22.1	157/353	44.5
> 7.0 cm	20/118	17.0	672/3087	21.8	354/756	46.8
Total	930/16735	5.6	11873/89460	13.3	1732/3769	46.0

LN: lymph node; pN+: pathologically node-positive.

Table 4. Multivariable logistic regression analysis for factors associated with the discovery of pathologic nodal involvement at surgery.

Parameter	All patients		Sublobar & lobectomy only
	OR (95% CI)	p Value	OR (95% CI)	p Value
Age (years)	0.995 (0.993–0.997)	<.001	0.994 (0.992–0.996)	<.001
Gender
Male	Ref	Ref	Ref	Ref
Female	0.905 (0.872–0.939)	<.001	0.906 (0.872–0.915)	<.001
Race
White	Ref	Ref	Ref	Ref
Black	0.960 (0.898–1.027)	.239	0.975 (0.909–1.045)	.475
Other	1.193 (1.079–1.319)	.001	1.205 (1.087–1.336)	<.001
Charlson Deyo score
0	Ref	Ref	Ref	Ref
1	0.965 (0.927–1.004)	.082	0.943 (0.904–0.983)	.005
2	0.925 (0.871–0.983)	.011	0.910 (0.855–0.969)	.003
≥3	0.949 (0.856–1.052)	.319	0.900 (0.809–1.002)	.055
Facility type
Academic	Ref	Ref	Ref	Ref
Non-academic	0.995 (0.958–1.035)	.819	1.035 (0.994–1.077)	.099
Not recorded	0.992 (0.699–1.407)	.962	0.843 (0.568–1.253)	.399
Histology
Adenocarcinoma	Ref	Ref	Ref	Ref
Squamous cell carcinoma	0.656 (0.630–0.682)	<.001	0.608 (0.583–0.633)	<.001
Tumor grade
Well differentiated	Ref	Ref	Ref	Ref
Moderately differentiated	2.414 (2.232–2.611)	<.001	2.441 (2.252–2.646)	<.001
Poorly differentiated	2.934 (2.708–3.178)	<.001	3.003 (2.766–3.260)	<.001
Not recorded	2.415 (2.141–2.724)	<.001	2.456 (2.172– 2.778)	<.001
Tumor size (cm)	1.099 (1.090–1.108)	<.001	1.142 (1.132–1.530)	<.001
Surgery
Sublobar	Ref	Ref	–	–
Lobectomy	2.279 (2.124–2.445)	<.001	–	–
Pneumonectomy	10.575 (9.585–11.666)	<.001	–	–
Number of nodes removed	1.004 (1.004–1.005)	<.001	1.004 (1.004–1.005)	<.001
Days from diagnosis to surgery	1.009 (1.006–1.012)	<.001	1.010 (1.006–1.013)	<.001

OR: odds ratio; CI: confidence interval.

Bold indicates statistically significant p values.

Figure 1. Graph of the proportion of patients with occult lymph nodal positivity as a function of tumor size and grade for squamous cell carcinoma with (A) low grade disease; (B) intermediate grade disease and (C) high grade disease; and for patients with adenocarcinoma with (D) low grade disease; (E) intermediate grade disease and (F) high grade disease.