Care of patients with non-small-cell lung cancer stage III – the Central European real-world experience

	Patients(N = 583)
Procedure
	N (%)	range of % in centres
Chest CT scan	567 (97)	67 – 100
Chest X-ray	559 (96)	79 – 100
Bronchoscopy	521 (89)	65 – 100
Upper abdominal CT scan	389 (67)	0 – 100
Upper abdominal US	160 (27)	2 – 87
PET-CT or PET scan	163 (28)	0 – 78
Brain CT or MRI	117 (20)	0 – 91
Bone scan	88 (15)	0 – 79
EBUS or EUS	80 (14)	0 – 71
CT-guided biopsy	54 (9)	0 – 31
VATS	19 (3)	0 – 35
Mediastinoscopy	13 (2)	0 – 13
Others	47 (8)	0 – 30

Overall survival according to stage and treatment modalities

	N	Median	1-year	2-year	3-year
Characteristic
		Months (95% CI)		% (95% CI)
IIIA
Total*	321	20.0 (17.1; 21.4)	70.7 (65.9; 75.9)	39.4 (34.3; 45.2)	27.0 (21.8; 33.3)
Good	223	21.4 (20.1; 25.8)	76.3 (70.9; 82.1)	45.6 (39.4; 52.8)	33.8 (27.7; 41.3)
Poor	75	13.3 (11.4; 17.7)	57.3 (47.2; 69.7	23.2 (15.2; 35.2)	9.1 (3.2; 26.0)
IIIB
Total*	262	14.4 (13.0; 15.9)	58.2 (52.3; 64.5)	27.5 (22.5; 33.7)	13.5 (9.0; 20.2)
Good	146	17.8 (14.8; 19.6)	67.0 (59.8; 75.1)	33.1 (26.1; 42.0)	19.6 (13.2; 29.1)
Poor	97	10.4 (8.8; 19.6)	44.1 (35.2; 55.2)	17.3 (11.1; 27.0)	8.1 (3.0; 21.6)
T3N3 and T4N3**	84	11.6 (9.8; 15.9)	48.5 (38.8; 60.5)	22.6 (15.2; 33.8)	9.4 (3.9; 22.7)
IIIA+IIIB
Total*	583	16.8 (15.3; 18.5)	65.1 (61.3; 69.1)	34.1 (30.4; 38.2)	21.0 (17.3; 25.4)
Good	369	20.1 (18.0; 21.5)	72.6 (68.2; 77.3)	40.7 (35.9; 46.2)	28.3 (23.6; 34.0)
Poor	172	11.8 (10.2; 14.2)	50.0 (42.9; 57.9)	19.9 (14.6; 27.0)	8.0 (3.6; 17.8)
Surgery
All surgeries	135	29.0 (27.1; NA)	82.2 (76.0; 88.9)	60.6 (52.8; 69.6)	43.9 (35.2; 54.8)
Alone	9	13.9 (3.2; NA)	55.6 (31.0; 99.7)	22.2 (6.6; 75.4)	22.2 (6.6; 75.4)
Surgery plus CT or RT	85	27.8 (23.6; NA)	80.0 (71.9; 89.0)	57.2 (47.5; 68.9)	37.0 (26.7; 51.3)
Surgery plus adjuvant CT	77	28.3 (24.7; NA)	81.8 (73.6; 90.9)	60.6 (50.6; 72.7)	38.9 (28.0; 54.0)
Trimodality therapy	41	Not reached	92.7 (85.0; 100)	76.9 (64.7; 91.5)	64.8 (49.9; 84.2)
Non-surgical therapy
All non-surgical	448	14.6 (13.7; 15.9)	59.9 (55.5; 64.7)	26.0 (22.1; 30.5)	13.8 (10.2; 18.8)
CT alone	150	12.7 (11.3; 13.9)	56.5 (49.1; 65.0)	19.1 (13.7; 26.8)	6.2 (2.7; 14.4)
RT alone	69	12.7 (9.6; 18.4)	52.2 (41.6; 65.4)	18.8 (11.6; 30.7)	11.8 (5.9; 23.5)
CRT all	200	19.6 (17.5; 21.6)	72.9 (67.0; 79.3)	36.9 (30.7; 44.5)	22.6 (16.1; 31.6)
CRT sequential	146	20.5 (17.2; 22.8)	75.2 (68.5; 82.5)	38.8 (31.5; 47.9)	23.5 (16.2; 34.0)
CRT concurrent	54	17.9 (14.6; 22.2)	66.7 (55.2; 80.5)	32.0 (21.6; 47.6)	22.5 (12.7; 39.9)
			HR (95% CI)	p-value
IIIA vs. IIIB			0.70 (0.58; 0.85)	< 0.001
IIIA Good vs. IIIA Poor			0.54 (0.40; 0.73)	< 0.001
IIIB Good vs. IIIB Poor			0.57 (0.43; 0.76)	< 0.001
IIIA vs. IIIB Good			0.86 (0.68; 1.09)	0.212
Tri-modality vs. Surgery plus adjuvant CT			0.47 (0.25; 0.89)	0.021
CRT sequential vs. concurrent			0.83 (0.57; 1.20)	0.326

TNM subgroups (Union for International Cancer Control [UICC] 7)

	Total patient population		Patients undergoing surgery
TNM
	N (%)	N	% of total population	% in stage subgroup
IIIA+IIIB	583 (100)	135	32.2	NA
IIIA	321 (55.1)	119	20.4	37.1
T4N0	33 (5.7)	10	1.7	30.3
T3N1	39 (6.7)	16	2.7	41.0
T4N1	26 (4.5)	7	1.2	26.9
T1N2	25 (4.3)	14	2.4	56.0
T2N2	98 (16.8)	45	7.7	45.9
T3N2	100 (17.2)	27	4.6	27.0
IIIB	262 (44.9)	16	2.8	6.1
T4N2	129 (22.2)	15	2.6	11.6
T1N3	17 (2.9)		0	0
T2N3	32 (5.5)		0.2	3.1
T3N3	29 (5.0)
T4N3	55 (9.4)
T stage
T1	42 (7.2)	14	2.4	33.3
T2	130 (22.3)	46	7.9	35.4
T3	168 (28.8)	43	7.4	25.6
T4	243 (41.7)	32	5.5	13.1
N stage
N0	33 (5.7)	10	1.7	30.3
N1	65 (11.1)	23	3.9	35.4
N2	352 (60.4)	101	17.3	28.7
N3	133 (22.8)	1	0.2	0.8

Therapeutic modalities and combinations

Therapeutic modalities	IIIA (N=321)	IIIB (N 262) N=(%)	IIIA+IIIB (N=583)
Any combination	207 (64.5)	119 (45.4)	326 (55.9)
Surgery	119 (37.1)	16 (6.1)	135 (23.2)
Surgery alone	9 (2.8)	0	9 (1.5)
Surgery plus radiotherapy	7 (2.2)	1 (0.4)	8 (1.4)
Surgery plus chemotherapy	70 (21.8)	7 (2.7)	77 (13.2)
Preoperative chemotherapy	22 (6.9)	4 (1.5)	26 (4.4)
Perioperative chemotherapy	3 (0.9)	0	3 (0.5)
Adjuvant chemotherapy	45 (14.0)	3 (1.1)	48 (8.2)
Surgery plus RT plus CT (trimodality)	33 (10.3)	8 (3.1)	41 (7.0)
Sequential preoperative RT plus CT	2 (0.6)	0	2 (0.3)
Concurrent preoperative RT plus CT	3 (0.9)	1 (0.4)	4 (0.7)
Sequential postoperative RT plus CT	23 (7.2)	3 (1.1)	26 (4.5)
Concurrent postoperative RT plus CT	5 (1.6)	4 (1.5)	9 (1.5)
Thoracic RT (including other modalities)	174 (54.2)	144 (55.0)	318 (54.6)
Radiotherapy alone	37 (11.5)	32 (12.2)	69 (11.8)
Chemoradiotherapy	97 (30.2)	103 (39.3)	200 (34.3)
Sequential	74 (23.1)	72 (27.5)	146 (25.0)
Concurrent	23 (7.2)	31 (11.8)	54 (9.3)
Chemotherapy (including other modalities)	256 (79.7)	212 (80.9)	468 (80.3)
Chemotherapy alone	58 (18.1)	92 (35.1)	150 (25.7)
Best supportive care alone	9 (2.8)	20 (7.6)	29 (5.0)
Type of surgery	IIIA (N = 119)	IIIB (N = 16)	IIIA+IIIB (N = 135)
Lobectomy	74 (62.3)	3 (18.7)	77 (57.0)
Bi-lobectomy	6 (5.0)	0	6 (4.5)
Pneumonectomy	28 (23.5)	4 (25.0)	32 (23.7)
Atypical radical resection	5 (4.2)	1 (6.2)	6 (4.5)
Non-radical surgery*	6 (5.0)	8 (50.0)	14 (10.4)

Progression free survival according to stage and risk groups

		Progression-free survival

Characteristic	N	Median	1-year	2-year	3-year

		Months (95% CI)		% (95% CI)
IIIA
Total*	321	12.5 (11.3; 13.6)	52.9 (47.7; 58.7)	24.1 (19.8; 29.3)	16.8 (13.0; 21.7)
Good	223	12.9 (12; 15.2)	55.8 (49.6; 62.7)	27.6 (22.3; 34.3)	19.6 (14.8; 26.0)
Poor	75	11.4 (7.9; 13.2)	45.3 (35.4; 58.1)	14.2 (8.1; 25.0)	8.3 (3.8; 18.1)
IIIB
Total*	262	9.9 (9.2; 10.8)	38.5 (33.1; 44.9)	12.8 (9.3; 17.7)	4.3 (1.8; 9.9)
Good	146	10.7 (9.6; 12.6)	43.8 (36.5; 52.6)	13.6 (9.0; 20.8)	8.6 (4.7; 15.5)
Poor	97	8.6 (7.8; 9.9)	26.8 (19.3; 37.2)	9.9 (5.4; 18.2)	0
T3N3 and T4N3**	84	9.4 (7.9; 11.3)	34.5 (25.7; 46.3)	10.7 (5.8; 20.0)	2.5 (0.4; 15.1)
IIIA+IIIB
Total*	583	11.2 (10.2; 12.2)	46.5 (42.6; 50.7)	19.0 (16.0; 22.6)	11.5 (8.9; 14.9)
Good	369	12.2 (11.0; 13.3)	51.0 (46.2; 56.4)	22.1 (18.2; 26.9)	15.4 (11.9; 19.9)
Poor	172	9.2 (8.3; 10.5)	34.9 (28.4; 42.8)	11.7 (7.7; 17.7)	3.7 (1.3; 10.8)
		HR (95% CI)	p-value
IIIA vs IIIB		0.71 (0.59; 0.85)	< 0.001
IIIA Good vs IIIA Poor		0.69 (0.52; 0.92)	0.011
IIIB Good vs IIIB Poor		0.69 (0.53; 0.90)	0.006
IIIA vs IIIB Good		0.80 (0.65; 0.99)	0.037

Overall survival according to diagnostic variables

					Survival

			Median	Univariate analysis	P-value	Multivariate analysis
Variable		N					P-value
			months (95% CI)	HR (95% Wald CI)		HR (95% Wald CI)
Stage	IIIA	321	20.0 (17.1; 21.4)		IIIA vs. IIIB:
	IIIB	262	14.4 (13.0; 15.9)	0.70 (0.58; 0.85)	< 0.001	0.77 (0.62;0.95)	0.017
Gender	Female Male	188 395	20.4 (16.8; 23.8) 15.4 (14.3; 17.6)	0.76 (0.62; 0.94)	Femalevs . male: 0.010	0.78 (0.64;0.96)	0.044
Smoking	Current smoker	308	15.3 (14.2; 17.7)		Never-smokers	vs:
status	Former smoker	219	18.9 (15.9; 20.6)	Current: 0.54 (0.34; 0.84)	0.007	Current: 0.71 (0.42;0.22)	0.218
	Never smoker	42	27.1 (17.0; NA)	Former: 0.61 (0.39; 0.97)	0.036	Former: 0.75 (0.44;1.30)	0.308
Weight loss	No	406	20.0 (17.9; 21.1)		No vs. yes:
≥ 10%	Yes	120	12.7 (10.8; 14.8)	0.54 (0.43; 0.68)	< 0.001	0.68 (0.53;0.88)	0.003
		146	22.4 (17.7; 26.1)	0 vs. ≥ 2: 0.37 (0.28; 0.50)	< 0.001	0.62 (0.43;0.88)	0.007
PS		338	15.4 (13.9; 17.2)	1 vs. ≥ 2: 0.52 (0.41; 0.66)	< 0.001	0.69 (0.52;0.91)	0.009
	≥2	99	11.6 (8.8; 14.7)	0 vs. 1: 0.72 (0.57; 0.92)	0.007	0.90 (0.68;1.17)	0.422
	Squamous	309	16.3 (15.0; 19.0)		Adeno vs.:
Histology	Adenoca	220	18.1 (14.7; 20.6)	Squam: 0.96 (0.79; 1.18)	0.726	Squam: 0.93(0.68;1.26)	0.630
	NOS/others	54	15 (10.1; 20.1)	NOS/oth: 0.79 (0.57; 1.11)	0.18	NOS/oth:0.96(0.63;1.48)	0.857
EGFR	Positive	14	27.1 (20.3; NA)		Positive vs:
mutation	Negative	128	15.8 (13.9; 19.7)	Negative: 0.51 (0.24; 1.10)	0.087	Negative:0.57(0.25;1.28)	0.176
positivity	Not tested	441	16.5 (15.0; 18.9)	Not tested: 0.52 (0.25; 1.10)	0.087	Not tested:0.83(0.36;1.89)	0.651
Nodes	No	411	14.4 (13.3;15.9)		Yes vs. no:
confirmed	Yes	172	24.7 (21.0; 28.8)	0.56 (0.45; 0.70)	< 0.001	0.67 (0.52;0.87)	0.002
PET-CT or	Yes	163	19.6 (17.8; 22.8)		Yes vs. no:
PET scan	No	420	15.4 (14.1; 17.6)	0.73 (0.58–0.91)	0.005	0.84 (0.66;1.07)	0.160

Patient characteristics

	IIIA (N = 321)	IIIB (N = 262)	IIIA + IIIB (N = 583)
Characteristic				P *
	N (%)	N (%)	N (%)
Age
< 65 years	155 (48.3)	117 (44.7)	272 (46.7)
≥ 65 years	166 (51.7)	145 (55.3)	311 (53.3)
Mean ± SD (years)	64.8 ± 10.5	65.1 ± 10.1	64.9 ± 10.3	0.429
Median (years)	65.4	66.0	65.6
Gender
Female	92 (28.7)	96 (37.0)	188 (32.2)
Male	229 (71.3)	166 (63.6)	395 (67.8)	0.050
Smoking status
Current smoker	161 (50.2)	147 (56.3)	308 (52.8)
Former smoker	127 (39.6)	92 (35.2)	219 (37.6)
Never smoker	26 (8.1)	16 (6.1)	42 (7.2)
Unknown	7 (2.2)	7 (2.7)	14 (2.4)	0.446
Weight loss ≥10% within prior three months
No	243 (75.7)	163 (62.5)	406 (69.6)
Yes	50 (15.6)	70 (26.8)	120 (20.6)
Unknown	28 (8.7)	29 (11.0)	57 (9.8)	<0.001
WHO performance status
0	86 (26.8)	60 (23.0)	146 (25.0)
1	194 (60.4)	144 (54.9)	338 (58.0)
2	31 (9.7)	41 (15.7)	72 (12.3)
3	10 (3.1)	17 (6.5)	27 (4.6)	0.025
Histology
Squamous cell carcinoma	176 (54.8)	133 (51.0)	309 (53.0)
Adenocarcinoma	115 (35.8)	105 (40.0)	220 (37.7)
NSCLC NOS	18 (5.6)	18 (6.9)	36 (6.2)
Other	12 (3.7)	6 (2.3)	18 (3.1)	0.477

eISSN:: 1581-3207
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Care of patients with non-small-cell lung cancer stage III – the Central European real-world experience

Article Category: Research Article

Published Online: May 28, 2020

Page range: 209 - 220

Received: Jan 09, 2020

Accepted: Apr 14, 2020

DOI: https://doi.org/10.2478/raon-2020-0026

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

Figure 2

Figure 3

Figure 4

Diagnostic procedures

Overall survival according to stage and treatment modalities

TNM subgroups (Union for International Cancer Control [UICC] 7)

Therapeutic modalities and combinations

Progression free survival according to stage and risk groups

Overall survival according to diagnostic variables

Patient characteristics