Lung cancer screening: Should we be excluding people with previous malignancy?

Table 1 Index trials of lung cancer screening

Ref.	Participants	Exclusion criteria	Design	Results
Aberle et al[5]	53454 participants	Previous lung cancer diagnosis	Randomized Control Trial	Rate of positive screening was 24.2% in LDCT and 6.9% with CXR group
	Age 55 to 74
	At least 30 pack-year smoking history	CT scan within previous 18 mo	Participants randomized to three annual screenings with LDCT (26722) vs single view PA CXR (26732)	The majority of positive screening results were false positives, 96.4% in the LDCT group and 94.5% in the CXR group
	Former smokers must have quit within previous 15 yr			Lung cancer mortality decreased by 20% (P = 0.004) and all cause mortality decreased by 6.7% in LDCT group (P = 0.02)
van Iersel et al[14]	15822 participants	Hemoptysis or unexplained weight loss of 15 lbs or more in last year	Randomized Control Trial	Ongoing - 10 yr follow up planned
	Age 50-74	Current or past diagnosis of renal cancer, melanoma or breast cancer
	Determined to be high risk based on answers to heath questionnaire	Lung cancer diagnosis within last 5 yr or current treatment	Participants randomized to either LDCT screening (7915) or no screening (7907)
	Good overall health (able to climb 2 flights of stairs, weight less than 140 kg)	CT scan within past year
Infante et al[16]	2472 participants	History of previous malignancy treated within 10 yr (exceptions: Early laryngeal cancer and nonmelanoma skin cancer with a 5-yr disease-free interval)	Randomized Control Trial	Ongoing. 3 yr results: Lung cancer detected in 4.7% of patients in LDCT group and 2.8% in controls (P = 0.016)
	Males aged 60-74
	20 pack-year smoking history	Comorbid conditions with life expectancy less than 5 yr	Randomized to 5 yr of annual screening with LDCT (1276) or clinical follow up (1196)	There was a 1.6% lung cancer mortality in the LDCT group and 1.7% in the control group (P = 0.84). No difference in all cause mortality (P = 0.83) to this point in the study
Saghir et al[22]	4104 participants	Previous cancer diagnosis and treatment	Randomized control trial	There was a higher rate of invasive procedures performed in the LDCT group compared with controls (P < 0.0001)
	Age 50-70			Ongoing. 5 yr results:
	At least 20 pack-year smoking history	Comorbid illness that would shorten life expectancy to < 10 yr	Participants randomized to five annual LDCT screenings (2052) or no screening (2052)	Lung cancer was diagnosed in 69 patients in the LDCT group, compared with 24 in the control group (P < 0.001)
	Former smokers who quit after age 50 and quit less than 10 yr prior	CT scan within previous year		Stage I-IIB lung cancer was diagnosed more frequently in the LDCT group (P = 0.002), however there was no difference in frequency of Stage IIIA-IV lung cancer (P = 0.509)
	FEV1 of at least 30% predicted value			There was no difference in mortality from lung cancer (P = 0.428) or overall mortality (P = 0.059) to this point of follow up
	Good overall health (able to climb 2 flights of stairs, weight less than 130 kg)
Pastorino et al[23]	4099 participants	History of cancer within the previous 5 yr	Randomized Control Trial	The cumulative 5-yr lung cancer incidence rate was 0.0031% in the control group, 0.0046% in the biennial, and 0.0062% in the annual LDCT group (P = 0.036)
	Age 49 or older
	At least 20 pack-year smoking history - current smoker or had quit within 10 yr		Randomized participants to annual LDCT screening (1190), biennial LDCT screening (1186), or observation alone (1723)	Rates of mortality from lung cancer were 0.0011% in the control group, 0.0011% in the biennial group, and 0.0022% in the annual group (P = 0.21)
				There was also no difference in all cause mortality between the three groups (P = 0.13)

LDCT: Low dose CT; CXR: Chest radiography; CT: Computed tomography.

Table 2 Prior malignancy and lung cancer

Prior malignancy	Ref.	Method	Results
Lung	Lou et al[38]	1294 participants with early-stage NSCLC underwent resection and then were followed with surveillance CT screening	Recurrence was diagnosed in 20% of patients and second primary lung cancer was diagnosed 7% of patients. The risk of second primary lung cancer diagnosis did not decrease over time
			Of the second primary cancers that were diagnosed, 93% were identified by scheduled surveillance CT. Of the recurrences that were diagnosed, 61% were identified by surveillance CT. Twenty five percent of patients required additional invasive testing, but less than 1% experienced complications from these procedures
Head and Neck	Milano et al[50]	61883 patients with SCC of the head and neck were identified via the SEER database. Of those, 4522 developed a second primary lung cancer. A retrospective data analysis was performed	The risk of developing a primary lung cancer after HNSCC was 5.8%, 11.4%, and 16.4% at 5, 10, and 15 yr
			These rates are higher compared to the general population
Head and Neck	Baxi et al[51]	35958 three-year survivors of SCC of the head and neck were identified via SEER database. A competing-risks proportional hazards regression was used to estimate probabilities of death from different causes	Second primary malignancy was the second leading cause of death (second only to primary head and neck squamous cell carcinoma) in this population Of these, 53% of second primary malignancies were lung cancer
Head and Neck	Pagedar et al[54]	Data was collected and retrospectively analyzed. Survival estimates were generated for patients with lung cancer with and without a history of head and neck cancer	The median survival of patients with only primary lung cancer was 38 mo, compared to 22 mo in those with a history of head and neck cancer with lung cancer as a second primary malignancy. This statistically significant difference suggests that survival outcomes after lung cancer diagnosis are worse in patients who have a history of head and neck malignancy
Breast	Kitada et al[63]	Data was collected an analyzed on 1226 patients who underwent surgical resection of breast cancer, 49 of whom were found to have at lease one pulmonary lesion during or after workup	14 patients underwent surgical resection of the pulmonary lesion. Primary lung cancer was the diagnoses in 3 of these patients, metastases in 8 cases. Of those diagnosed with second primary lung cancer, the stage was IA in all
Breast	Kerendi et al[67]	35 patients with breast cancer and second primary lung cancer were identified and retrospective analysis of survival was performed	More than half of patients had their lung cancer diagnosed during workup or follow-up. 54% of these patients were successfully treated with surgery. There was a statistically significant survival benefit when the cancer was detected early (stage IA, asymptomatic)
Breast	Milano et al[68]	3529 women with NSCLC diagnosis after breast treatment were identified in the SEER database. Data on these patients was retrospectively analyzed and compared to data on 151628 women diagnosed with NSCLC alone	Patients with a history of breast cancer were diagnosed at significant earlier stage, although surgical resection was used more frequently in the NSCLC only group
			History of breast cancer history did not affect overall survival in localized NSCLC. Overall survival was significantly greater in patients with regional and distant NSCLC that had a history of breast cancer
Bladder	del Rey et al[72]	Data from 231 patients with non-muscle invasive bladder cancer were retrospectively analyzed	Lung cancer was the most common second primary malignancy in this population. The risk of lung cancer in patients with non-muscle invasive bladder cancer is 10 fold higher than the regional general population
Lymphoma	Das et al[75]	Authors used a decision-analytic model to estimate potential benefits of annual low-dose CT screening vs no screening in a hypothetical cohort of patients (early stage lymphoma diagnosed at age 25, lung cancer screening starting at age 30). Model parameters were generated from SEER	In this simulated model, annual CT screening increased survival by 0.64 yr for smokers and 0.16 yr for non-smokers. The difference in quality of life and cost effectiveness was also more pronounced in smokers
Lymphoma	Milano et al[77]	Survival data of 187 patient with history of Hodgkins lymphoma diagnosed with NSCLC was compated to data from 178431 patients diagnosed with NSCLC only	Hodgkins lymphoma survivors had significantly inferior overall survival across all lung cancer stages (estimated to be between 30% to 60% decrease in overall survival)
			Patients with younger age at lymphoma diagnosis, younger age at lung cancer diagnoses, and those with longer latency between cancer diagnoses were more likely to be diagnosed with late stage disease
Colorectal	Hattori et al[34]	A retrospective analysis of lung cancer patients with (123) or without (4431) a previous history of colorectal cancer treated with surgical resection	There is no statistically significant difference in overall survival comparing patients with lung cancer vs lung cancer with a history of surgery for colorectal cancer. Prior history of colorectal cancer was not a poor prognostic indicator on multivariate analysis
			Of those patients who had been diagnosed with both lung and colorectal cancer, those who are older and those who underwent treatment with adjuvant chemotherapy had poorer outcomes

CT: Computed tomography; NSCLC: Non-small-cell lung cancer; SEER: Surveillance, epidemiology and end results; SCC: Squamous cell cancer; HNSCC: Head and neck squamous cell cancer.