Primary site surgery for elderly patients with distant metastatic pancreatic neuroendocrine tumor: to do or not to do?

Figures & data

Figure 1 Patient screening process.

Abbreviations: pNET, pancreatic neuroendocrine tumor; SEER, Surveillance Epidemiology and End Results.

Table 1 Characteristics of patients older than 65 years included in the study

Variables	Before PSM			After PSM
	NPSS, N=148	PSS, N=62	p	NPSS, N=62	PSS, N=62	p
Age			0.265			0.091
65–75 years	95 (64.2%)	45 (72.6%)		35 (56.5%)	45 (72.6%)
≥75 years	53 (35.8%)	17 (27.4%)		27 (43.5%)	17 (27.4%)
Gender			0.049			0.281
Male	89 (60.1%)	28 (45.2%)		35 (56.5%)	28 (45.2%)
Female	59 (39.9%)	34 (54.8%)		27 (43.5%)	34 (54.8%)
Race			0.247			0.161
White	123 (83.1%)	57 (91.9%)		50 (80.6%)	57 (91.9%)
Black	16 (10.8%)	3 (4.8%)		9 (14.5%)	3 (4.8%)
Other	9 (6.1%)	2 (3.2%)		3 (4.8%)	2 (3.2%)
Marital status			0.639			0.855
Married	96 (64.9%)	38 (61.3%)		36 (58.1%)	38 (61.3%)
Unmarried	52 (35.1%)	24 (38.7%)		26 (41.9%)	24 (38.7%)
Year of diagnosis			0.875			0.699
1973–2009	53 (35.8%)	21(33.9%)		18 (29.0%)	21 (33.9%)
2010–2015	95 (64.2%)	41 (66.1%)		44 (71.0%)	41 (66.1%)
Tumor site			0.006			0.517
Head	58 (39.2%)	12 (19.4%)		16 (25.8%)	12 (19.4%)
Body/tail	62 (41.9%)	42(67.7%)		35 (56.5%)	42 (67.7%)
Overlap	21 (14.2%)	7 (11.3%)		8 (12.9%)	7 (11.3%)
Other	7 (4.7%)	1 (1.6%)		3 (4.8%)	1 (1.6%)
Tumor size			0.000			0.097
≤4 cm	48 (32.4%)	21 (33.9%)		29 (46.8%)	21 (33.9%)
>4 cm	67 (45.3%)	41 (66.1%)		31 (50.0%)	41 (66.1%)
Unknown	33 (22.3%)	0 (0%)		2 (3.2%)	0 (0%)
Histological grade			0.032			1.000
Well/moderately	97(65.5%)	50 (80.6%)		50 (80.6%)	50 (80.6%)
Poorly/undifferentiated	51(34.5%)	12 (19.4%)		12 (19.4%)	12 (19.4%)

Notes: Race: other included American Indian/AK, Native Asian/Pacific Islander. Marital status: unmarried included divorced/separated/single (never married)/unmarried or domestic partner/widowed. Tumor site: “Other” included Islets of langerhans+other specific parts of pancreas+NOS of pancreas.

Abbreviations: PSM, propensity score matching; NPSS, no primary site surgery; PSS, primary site surgery; cm, centimeter.

Table 2 Logistic regression analysis of characteristics for PSS in elderly patients (≥65 years)

Variables	Univariate analysis for PSS			Multivariate analysis for PSS
	OR	95% CI	p	OR	95% CI	p
Age
65–75 years	1 (Referent)
>75 years	0.677	0.353–1.299	0.241
Gender
Male	1 (Referent)			1 (Referent)
Female	1.832	1.007–3.333	0.048	2.329	1.204–4.503	0.012
Race
White	1 (Referent)
Black	0.405	0.113–1.444	0.163
Other	0.480	0.100–2.291	0.357
Marital status
Married	1 (Referent)
Unmarried	1.166	0.632–2.151	0.623
Year of diagnosis
1973–2009	1 (Referent)
2010–2015	1.089	0.584–2.033	0.788
Tumor site
Head	1 (Referent)			1 (Referent)
Body/tail	3.274	1.570–6.826	0.002	3.780	1.749–8.170	0.001
Overlap	1.611	0.560–4.638	0.377	1.241	0.418–3.681	0.697
Other	0.690	0.078–6.142	0.740	0.711	0.077–6.535	0.763
Histological grade
Well/moderately	1 (Referent)			1 (Referent)
Poorly/undifferentiated	0.456	0.223–0.934	0.032	0.455	0.215–0.964	0.040
Tumor size
≤4 cm	1 (Referent)
>4 cm	1.399	0.735–2.662	0.485
Unknown			NA

Note: Variables with univariate analysis p<0.1 underwent further multivariate analysis.

Abbreviation: PSS, primary site surgery.

Table 3 Multivariate regression analysis of characteristics for survival in elderly patients (≥65 years) before PSM

Variables	Multivariate analysis for OS			Multivariate analysis for CSS
	HR	95% CI	p	HR	95% CI	p
Age
65–75 years	1 (Referent)			1 (Referent)
>75 years	1.373	0.954–1.977	0.088	1.231	0.775–1.955	0.378
Gender
Male	1 (Referent)			1 (Referent)
Female	1.028	0.678–1.557	0.898	0.939	0.571–1.544	0.803
Race
White	1 (Referent)			1 (Referent)
Black	1.367	0.726–2.572	0.333	1.333	0.621–2.859	0.460
Other	1.598	0.782–3.269	0.199	1.767	0.777–4.018	0.175
Marital status
Married	1 (Referent)			1 (Referent)
Unmarried	1.228	0.852–1.770	0.271	1.417	0.906–2.217	0.127
Year of diagnosis
1973–2009	1 (Referent)			1 (Referent)
2010–2015	0.931	0.634–1.365	0.714	1.027	0.638–1.651	0.913
Tumor site
Head	1 (Referent)			1 (Referent)
Body/tail	1.104	0.734–1.661	0.635	0.872	0.538–1.415	0.580
Overlap	1.226	0.692–2.171	0.485	0.859	0.422–1.749	0.676
Other	1.709	0.784–3.729	0.178	1.758	0.773–3.997	0.178
Histological grade
Well/moderately	1 (Referent)			1 (Referent)
Poorly/undifferentiated	3.062	2.118–4.425	0.000	3.641	2.351–5.640	0.000
Tumor size
≤4 cm	1 (Referent)			1 (Referent)
>4 cm	0.862	0.568–1.308	0.485	0.790	0.476–1.310	0.361
Unknown	0.798	0.463–1.375	0.416	0.812	0.423–1.558	0.531
Primary site surgery
No	1 (Referent)			1 (Referent)
Yes	0.392	0.252–0.612	0.000	0.362	0.206–0.637	0.000

Note: Variables with univariate analysis p<0.1 underwent further multivariate analysis.

Abbreviations: OS, overall survival; CSS, cancer-specific survival; PSM, propensity score matching.

Table 4 Multivariate regression analysis of characteristics for survival in elderly patients (Table 4: Multfter PSM)

Variables	Multivariate analysis for OS			Multivariate analysis for CSS
	HR	95% CI	p	HR	95% CI	p
Age
65–75 years	1 (Referent)			1 (Referent)
>75 years	1.442	0.852–2.442	0.173	1.224	0.648–2.311	0.533
Gender
Male	1 (Referent)			1 (Referent)
Female	1.591	0.880–2.877	0.125	1.378	0.688–2.758	0.366
Race
White	1 (Referent)			1 (Referent)
Black	1.371	0.602–3.124	0.452	1.031	0.377–2.817	0.953
Other	2.705	0.959–7.628	0.060	3.864	1.340–11.143	0.012
Marital status
Married	1 (Referent)			1 (Referent)
Unmarried	1.309	0.750–2.288	0.344	1.370	0.694–2.703	0.364
Year of diagnosis
1973–2009	1 (Referent)			1 (Referent)
2010–2015	0.909	0.482–1.714	0.769	0.931	0.413–2.100	0.863
Tumor site
Head	1 (Referent)			1 (Referent)
Body/tail	0.649	0.347–1.214	0.176	0.664	0.303–1.456	0.307
Overlap	0.694	0.288–1.670	0.414	0.530	0.164–1.706	0.287
Other	0.423	0.129–1.384	0.155	0.602	0.167–2.171	0.438
Histological grade
Well/moderately	1 (Referent)			1 (Referent)
Poorly/undifferentiated	4.020	2.203–7.336	0.000	6.574	3.261–13.251	0.000
Tumor size
≤4 cm	1 (Referent)			1 (Referent)
>4 cm	1.058	0.618–1.813	0.836	1.087	0.548–2.157	0.811
Unknown	0.701	0.114–4.324	0.702	1.070	0.162–7.080	0.944
Primary site surgery
No	1 (Referent)			1 (Referent)
Yes	0.212	0.125–0.360	0.000	0.210	0.110–0.403	0.000

Note: Variables with univariate analysis p<0.1 underwent further multivariate analysis.

Abbreviations: OS, overall survival; CSS, cancer-specific survival; PSM, propensity score matching.

Figure 2 Overall survival and cancer-specific survival in elderly patients (≥65 years) with metastatic pNET who underwent primary site surgery (PSS) and no primary site surgery (NPSS), before and after propensity score matching (PSM).

Notes: (A) Kaplan–meier analysis for overall survival in elderly patients (≥65 years) who underwent PSS and NPSS before PSM; (B) Kaplan–meier analysis for cancer-specific survival in elderly patients (≥65 years) who underwent PSS and NPSS before PSM; (C) Kaplan–meier analysis for overall survival in elderly patients (≥65 years) who underwent PSS and NPSS after PSM; (D) Kaplan–meier analysis for cancer-specific survival in elderly patients (≥65 years) who underwent PSS and NPSS after PSM.

Figure 3 Kaplan–Meier analysis of cancer-specific survival for elderly patients (≥65 years) in sub-groups.

Notes: (A) Kaplan–meier analysis for cancer-specific survival in patients with age between 65 and 74 years and tumor of well or moderately differentiation; (B) Kaplan–meier analysis for cancer-specific survival in patients with age ≥75 years and tumor of well or moderately differentiation; (C) Kaplan–meier analysis for cancer-specific survival in patients with age between 65 and 74 years and tumor of poorly differentiation or undifferentiation; (D) Kaplan–meier analysis for cancer-specific survival in patients with age ≥75 years and tumor of poorly differentiation or undifferentiation.

Table S1 Multivariate regression analysis of characteristics for cancer-specific survival in patients with age 65–74 years+ well or moderately differentiated

Variables	Multivariate analysis for CSS
	HR	95% CI	p
Gender
Male	1 (Referent)
Female	1.887	0.794–4.485	0.151
Race
White	1 (Referent)
Black	0.676	0.183–2.492	0.556
Other	0.919	0.111–7.615	0.937
Marital status
Married	1 (Referent)
Unmarried	1.677	0.736–3.823	0.219
Year of diagnosis
1973–2009	1(Referent)
2010–2015	2.286	0.944–5.534	0.068
Tumor site
Head	1 (Referent)
Body/tail	0.963	0.398–2.329	0.933
Overlap	1.266	0.415–3.863	0.679
Other	2.908	0.816–10.367	0.100
Tumor size
≤4 cm	1(Referent)
>4 cm	1.835	0.822–4.096	0.138
Unknown	0.620	0.216–1.782	0.375
Primary site surgery
No	1 (Referent)
Yes	0.142	0.053–0.379	0.000

Table S2 Multivariate regression analysis of characteristics for cancer-specific survival in patients with age ≥75 years+ well or moderately differentiated

Variables	Multivariate analysis for CSS		p
	HR	95% CI
Gender
Male	1 (Referent)
Female	1.899	0.270–13.335	0.519
Race
White	1 (Referent)
Black
Other	28.922	1.998–418.6	0.014
Marital status
Married	1 (Referent)
Unmarried	0.582	0.103–3.289	0.582
Year of diagnosis
1973–2009	1(Referent)
2010–2015	0.408	0.097–1.719	0.222
Tumor site
Head	1 (Referent)
Body/tail	2.483	0.447–13.785	0.307
Overlap
Other	17.690	0.918–340.8	0.057
Tumor size
≤4 cm	1 (Referent)
>4 cm	0.166	0.036–0.764	0.037
Unknown	1.213	0.179–8.215	0.843
Primary site surgery
No	1 (Referent)
Yes	1.150	0.130–10.165	0.900

Table S3 Multivariate regression analysis of characteristics for cancer-specific survival in patients with age 65–74 years+ poorly differentiated or undifferentiated

Variables	Multivariate analysis for CSS		p
	HR	95% CI
Gender
Male	1 (Referent)
Female	1.143	0.349–3.746	0.825
Race
White	1 (Referent)
Black	3.047	0.748–12.406	0.120
Other	0.656	0.066–6.505	0.719
Marital status
Married	1 (Referent)
Unmarried	1.444	0.520–4.014	0.481
Year of diagnosis
1973–2009	1 (Referent)
2010–2015	0.802	0.304–2.118	0.656
Tumor site
Head	1 (Referent)
Body/tail	0.914	0.330–2.531	0.863
Overlap	0.719	0.168–3.090	0.658
Other	0.760	0.068–8.540	0.824
Tumor size
≤4 cm	1 (Referent)
>4 cm	0.841	0.302–2.341	0.740
Unknown	0.986	0.285–3.413	0.983
Primary site surgery
No	1 (Referent)
Yes	0.621	0.174–2.218	0.463

Table S4 Multivariate regression analysis of characteristics for cancer-specific survival in patients with age ≥75 years+ poorly differentiated or undifferentiated

Variables	Multivariate analysis for CSS		p
	HR	95% CI
Gender
Male	1 (Referent)
Female	0.640	0.141–2.898	0.563
Race
White	1 (Referent)
Black
Other	8.373	1.036–67.700	0.046
Marital status
Married	1 (Referent)
Unmarried	1.562	0.316–7.708	0.584
Year of diagnosis
1973–2009	1 (Referent)
2010–2015	0.380	0.064–2.266	0.288
Tumor site
Head	1 (Referent)
Body/tail	2.483	0.447–13.785	0.307
Overlap
Other	17.690	0.918–340.8	0.057
Tumor size
≤4 cm	1 (Referent)
>4 cm	0.458	0.119–1.766	0.257
Unknown	5.879	0.296–116.8	0.245
Primary site surgery
No	1 (Referent)
Yes	0.469	0.091–2.407	0.364