Erectile Dysfunction After Surgical Treatment of Lung Cancer: Real-World Evidence

Figures & data

Figure 1 Flowchart of the patient enrollment process of the lung cancer and matched non-lung cancer cohorts.

Abbreviations: ED, erectile dysfunction; N, number.

Table 1 Demographic Status and Comorbidity Compared Between Cohorts with and without Lung Cancer

	Lung Cancer
Variables	With		Without
Individuals	6025	100.0%	24,100	100.0%
Age
40–54	990	16.4%	3960	16.4%
55–64	1518	25.2%	6072	25.2%
65–74	2110	35.0%	8440	35.0%
≥75	1407	23.4%	5628	23.4%
Income level (NT$)
0	1530	25.4%	6120	25.4%
1~15,840	1290	21.4%	5160	21.4%
15,841~25,000	1905	31.6%	7620	31.6%
≥25,000	1300	21.6%	5200	21.6%
Urbanization
I	1804	29.9%	7216	29.9%
II	2492	41.4%	9968	41.4%
III	1129	18.7%	4516	18.7%
IV	600	10.0%	2400	10.0%
Comorbidities
Hypertension	3739	62.1%	14,194	58.9%
Arthritis	2743	45.5%	9619	39.9%
COPD	2408	40.0%	3780	15.7%
Hyperlipidemia	2290	38.0%	8732	36.2%
CAD	2023	33.6%	6991	29.0%
Diabetes	1875	31.1%	7178	29.8%
Smoking-related disorder	1791	29.7%	3456	14.3%
Asthma	1577	26.2%	3595	14.9%
Stroke	1465	24.3%	6633	27.5%
Kidney disease	1209	20.1%	4560	18.9%
Anxiety	995	16.5%	3075	12.8%
Depression	663	11.0%	1863	7.7%
PAD	323	5.4%	1315	5.5%
Obesity	36	0.6%	167	0.7%
CCI (before index date)
0	181	3.0%	7336	30.4%
1–2	1081	17.9%	8752	36.3%
3–5	3106	51.6%	5817	24.1%
≥6	1657	27.5%	2195	9.1%
Median (Q1-Q3)	4	(3–6)	1	(0–3)
Medications
Nonsteroidal anti-inflammatory drugs	3563	59.1%	10,878	45.1%
Anti-hypertension drugs	2731	45.3%	10,792	44.8%
Benzodiazepines	2191	36.4%	5792	24.0%
ED diagnosis after index date	91	1.5%	403	1.7%
Non-organic ED	6	0.1%	36	0.1%
Organic ED	85	1.4%	367	1.5%
Follow-up duration (year)
Median (Q1-Q3)	2.79	(1.34–5.46)	5.16	(2.67–8.78)

Abbreviations: CCI, Charlson comorbidity index; COPD, chronic obstructive pulmonary disease; CAD, coronary artery disease; ED, erectile dysfunction; NT$, New Taiwan Dollar; PAD, peripheral arterial disease.

Figure 2 The cumulative incidence rate of erectile dysfunction (ED) in the lung cancer (solid line) and non-lung cancer (dashed line) cohorts by the end of the follow‐up duration. “*” denotes p < 0.05.

Abbreviation: ED, erectile dysfunction.

Table 2 Crude and Adjusted Incidence Rates of ED for Lung Cancer Patients Compared with Non-Lung Cancer Control

	ED Events	Person-Years	IR (95% CI)	IRR (95% CI)	p value	aIRR (95% CI)	p value
Control	403	142,523.7	28.28 (25.65–31.18)	reference		reference
Lung cancer	91	23,653.4	38.47 (31.33–47.25)	1.36 (1.08–1.71)	0.008*	1.34 (1.06–1.70)	0.014*

Notes: aIRR was adjusted for age, income level, urbanization, comorbidities and medications listed in Table 1. “*” denotes p < 0.05.

Abbreviations: aIRR, adjusted IRR; CI, confidence interval; ED, erectile dysfunction; IR, incidence rate, per 10,000-person-years; IRR, incidence rate ratio.

Table 3 Subgroup Analysis Based on Different Age and Comorbidity for the Risk of ED in Study Cohort

Clinical Variables		IRR (95% CI)		p value		aIRR (95% CI)		p value
Age (year)
40–54		2.07 (1.35–3.17)		0.001*		1.93 (1.21–3.06)		0.005*
55–64		1.26 (0.86–1.84)		0.235		1.19 (0.80–1.78)		0.390
65–74		0.84 (0.53–1.35)		0.474		0.96 (0.60–1.56)		0.875
≥75		1.71 (0.82–3.54)		0.150		1.60 (0.74–3.44)		0.231
Comorbidities
CAD
No		1.38 (1.05–1.81)		0.022		1.29 (0.97–1.73)		0.081
Yes		1.33 (0.89–2.00)		0.163		1.34 (0.88–2.04)		0.174
Stroke
No		1.30 (1.01–1.68)		0.042		1.25 (0.96–1.64)		0.097
Yes		1.50 (0.90–2.50)		0.119		1.68 (0.99–2.85)		0.053
COPD
No		1.30 (0.98–1.73)		0.069		1.19 (0.89–1.59)		0.236
Yes		2.03 (1.31–3.13)		0.002*		1.68 (1.07–2.65)		0.025*
Kidney disease
No		1.38 (1.08–1.77)		0.009*		1.36 (1.05–1.76)		0.019*
Yes		1.21 (0.65–2.24)		0.553		1.11 (0.59–2.10)		0.751
Hypertension
No		1.51 (1.06–2.16)		0.024*		1.36 (0.93–1.99)		0.108
Yes		1.27 (0.95–1.71)		0.109		1.26 (0.92–1.70)		0.145
Arthritis
No		1.45 (1.06–1.99)		0.021*		1.35 (0.97–1.88)		0.079
Yes		1.25 (0.90–1.74)		0.178		1.22 (0.87–1.72)		0.247
PAD
No		1.36 (1.08–1.72)		0.009*		1.35 (1.06–1.72)		0.015*
Yes		1.27 (0.37–4.39)		0.705		2.04 (0.54–7.65)		0.291
Asthma
No		1.35 (1.04–1.76)		0.025*		1.32 (1.01–1.74)		0.045*
Yes		1.44 (0.90–2.30)		0.126		1.40 (0.86–2.27)		0.176
Diabetes
No		1.31 (1.00–1.73)		0.053		1.25 (0.93–1.66)		0.135
Yes		1.47 (0.99–2.20)		0.058		1.53 (1.01–2.33)		0.046*
Hyperlipidemia
No		1.36 (0.99–1.86)		0.056		1.32 (0.94–1.84)		0.106
Yes		1.33 (0.96–1.85)		0.089		1.29 (0.92–1.82)		0.138
Depression
No		1.27 (0.99–1.63)		0.065		1.23 (0.95–1.60)		0.119
Yes		1.93 (1.09–3.42)		0.024*		1.84 (1.00–3.39)		0.050*
Anxiety
No		1.14 (0.87–1.50)		0.343		1.12 (0.84–1.49)		0.448
Yes		2.01 (1.32–3.06)		0.001*		2.18 (1.40–3.40)		0.001*
Smoking-related disorder
No		1.27 (0.97–1.66)		0.087		1.21 (0.92–1.60)		0.171
Yes		2.05 (1.28–3.29)		0.003		1.77 (1.08–2.90)		0.022*
Obesity
No		1.36 (1.08–1.71)		0.008		1.35 (1.06–1.71)		0.014*
Yes		1.24 (0.15–10.65)		0.842		0.00 (0.00–0.07)		0.001*
Medications
Nonsteroidal anti-inflammatory drugs
No use		1.71 (1.21–2.42)		0.003*		1.28 (0.89–1.84)		0.181
Use		1.30 (0.96–1.76)		0.088		1.25 (0.92–1.72)		0.159
Anti-hypertension drugs
No use		1.60 (1.19–2.16)		0.002*		1.42 (1.04–1.95)		0.028*
Use		1.13 (0.79–1.60)		0.506		1.14 (0.79–1.65)		0.476
Benzodiazepines
No use		1.49 (1.12–1.98)		0.006*		1.36 (1.01–1.82)		0.042*
Use		1.23 (0.84–1.81)		0.288		1.22 (0.82–1.83)		0.327

Notes: aIRR was estimated by competing risk model and adjusted for age, urbanization, income, comorbidities and medications listed in Table 1.“*” denotes p < 0.05.

Abbreviations: aIRR, adjusted incidence rate ratio; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CAD, coronary artery disease; ED, erectile dysfunction; IRR, incidence rate ratio; PAD, peripheral arterial disease.

Table 4 Analysis of Risk Factors for Developing ED Among Lung Cancer Patients

Clinical Variables	IRR (95% CI)	p value	aIRR (95% CI)	p value
Age (year, ref: ≥75)
40–54	3.69 (1.75–7.80)	0.001*	5.44 (2.25–13.15)	<0.001*
55–64	2.82 (1.35–5.89)	0.006*	3.62 (1.61–8.17)	0.002*
65–74	1.25 (0.57–2.75)	0.576	1.51 (0.67–3.39)	0.316
Income level (ref: 0)
1~15,840	0.98 (0.50–1.92)	0.946	1.03 (0.52–2.06)	0.930
15,841~25,000	1.11 (0.61–2.02)	0.726	1.19 (0.63–2.25)	0.599
≥25,000	1.73 (0.97–3.11)	0.065	0.85 (0.44–1.63)	0.616
Urbanization (ref: IV)
I	1.38 (0.67–2.87)	0.382	1.43 (0.65–3.13)	0.375
II	0.99 (0.48–2.04)	0.969	1.04 (0.48–2.23)	0.923
III	0.49 (0.19–1.27)	0.142	0.50 (0.19–1.31)	0.157
Comorbidities (ref: No)
CAD	0.90 (0.58–1.40)	0.634	0.99 (0.60–1.63)	0.971
Stroke	0.71 (0.42–1.19)	0.194	0.83 (0.47–1.48)	0.530
COPD	0.93 (0.61–1.41)	0.728	1.40 (0.85–2.30)	0.188
Kidney disease	0.63 (0.34–1.16)	0.137	0.82 (0.44–1.55)	0.547
Hypertension	0.86 (0.56–1.30)	0.469	1.42 (0.81–2.47)	0.217
Arthritis	1.05 (0.70–1.58)	0.818	1.36 (0.85–2.15)	0.196
PAD	0.56 (0.18–1.77)	0.324	0.78 (0.24–2.54)	0.682
Asthma	0.97 (0.61–1.54)	0.906	1.08 (0.66–1.79)	0.752
Diabetes	1.05 (0.68–1.63)	0.824	1.12 (0.69–1.80)	0.645
Hyperlipidemia	1.50 (1.00–2.27)	0.052	1.27 (0.80–2.00)	0.307
Depression	1.80 (1.06–3.05)	0.029*	1.62 (0.90–2.92)	0.107
Anxiety	2.50 (1.62–3.86)	<0.001*	2.99 (1.81–4.94)	<0.001*
Smoking-related disorder	1.05 (0.68–1.64)	0.816	1.22 (0.74–2.00)	0.432
Obesity	1.75 (0.24–12.58)	0.577	1.41 (0.19–10.39)	0.737
Medication (ref: 0–27 days)
Nonsteroidal anti-inflammatory drugs	0.56 (0.37–0.85)	0.006*	0.59 (0.37–0.95)	0.028*
Anti-hypertension drugs	0.61 (0.40–0.92)	0.020*	0.52 (0.30–0.90)	0.020*
Benzodiazepines	0.74 (0.48–1.13)	0.159	0.60 (0.36–0.98)	0.043*
Cancer related disease/treatment
CT/RT (ref: without CT/RT)
CT+RT	0.33 (0.16–0.67)	0.002*	0.40 (0.19–0.84)	0.015*
CT only	0.59 (0.34–1.01)	0.053	0.65 (0.38–1.14)	0.133
RT only	0.65 (0.30–1.42)	0.276	0.72 (0.33–1.59)	0.416
EGFR-TKI (ref: non-user)	0.24 (0.08–0.75)	0.014*	0.33 (0.10–1.08)	0.067

Note: “*” denotes p < 0.05.

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; CAD, coronary artery disease; CT, chemotherapy; ED, erectile dysfunction; EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor; NT$, New Taiwan Dollar; PAD, peripheral arterial disease; RT, radiotherapy; ref, reference.

Table 5 Incidence of ER Visiting and Admission in ED and Non-ED Lung Cancer Patients

	Patients	Events	Person-Years	IR (95% CI)	IRR (95% CI)	p value	aIRR (95% CI)	p value
ER visiting
Non-ED	5934	18,680	23,382.1	0.80 (0.79–0.81)	Reference		Reference
ED	91	403	327.5	1.23 (1.12–1.36)	1.54 (1.40–1.70)	<0.001*	2.19 (1.98–2.42)	<0.001*
Admission
Non-ED	5934	22,318	23,382.1	0.95 (0.94–0.97)	Reference		Reference
ED	91	225	327.5	0.69 (0.60–0.78)	0.72 (0.63–0.82)	<0.001*	1.11 (0.97–1.27)	0.119

Notes: aIRR was adjusted for age, income level, urbanization, comorbidities, medications and cancer-related treatments listed in Table 4. “*” denotes p < 0.05.

Abbreviations: aIRR, adjusted IRR; CI, confidence interval; ED, erectile dysfunction; IR, incidence rate, per person-years; IRR, incidence rate ratio.