https://links.lww.com/DCR/A922

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Supplementary Material Supplement Table 1: Surveillance strategies considered

Supplement Table 2: Effectiveness, cost, and incremental cost-effectiveness ratio for each surveillance strategy for individuals with a history of stage I colon cancer

Supplement Table 3: Effectiveness, cost, and incremental cost-effectiveness ratio for each surveillance strategy for individuals with a history of stage II colon cancer

Supplement Table 4: Effectiveness, cost, and incremental cost-effectiveness ratio for each surveillance strategy for individuals with a history of stage III colon cancer

Supplement Table 5: Optimal surveillance strategy at willingness to pay thresholds of $50,000 to $200,000 for patients with a history of stage I to III colon cancer using hazard rate of death for patients with unresectable metastases which was derived from the median survival of patients receiving FOLFOXIRI and bevacizumab ⁶⁵

Supplement Table 6: Strategies optimal in ≥10% of probabilistic sensitivity analysis iterations at a willingness to pay threshold of $100,000/QALY Supplement Figure 1a: Model predicted cumulative incidence of recurrence at 5 years compared to estimates from a population-based cohort study ^31,32

Supplement Figure 1b: Model predicted cumulative incidence of recurrence at 10 years compared to estimates from a population-based cohort study ^31,32

Supplement Figure 2a: Model predicted proportion of patients who undergo surgical treatment of recurrence compared to estimates from a randomized trial of intensive versus minimal surveillance strategies ⁶

Supplement Figure 2b: Model predicted 5-year overall survival compared to estimates from a population-based cohort study with median patient age of 71 years ⁶³

Supplement Figure 3a: Two-way sensitivity analysis displaying the optimal surveillance strategy at a willingness to pay threshold of (i)

$100,000/QALY and (ii) $200,000/QALY while varying the sensitivity and specificity of carcinoembryonic antigen testing for patients with a history of stage I colon cancer

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Supplement Figure 3b: Two-way sensitivity analysis displaying the optimal surveillance strategy at a willingness to pay threshold of (i)

$100,000/QALY and (ii) $200,000/QALY while varying the sensitivity and specificity of carcinoembryonic antigen testing for patients with a history of stage II colon cancer

Supplement Figure 3c: Two-way sensitivity analysis displaying the optimal surveillance strategy at a willingness to pay threshold of (i)

$100,000/QALY and (ii) $200,000/QALY while varying the sensitivity and specificity of carcinoembryonic antigen testing for patients with a history of stage III colon cancer

Supplement Figure 3d: Legend for Supplementary Figure 3

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Supplement Table 1: Surveillance strategies considered

Months since completion of initial curative treatment for colon cancer

Strategy Investigations 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60

Based on RCT (ref) 1:

Minimum/Symptom- based follow up

Clinic visit X X X X X

CEA¹

Liver ultrasound CT abdomen/pelvis Chest x-ray CT chest 2: CEA every 3 months

for 2 years then every 6 months for 3 years

Clinic visit X X X X X X X X X X X X X X

CEA¹ X X X X X X X X X X X X X X

Liver ultrasound CT abdomen/pelvis Chest x-ray CT chest 3: CT

chest/abdomen/pelvis every 6 months for 2 years then annually

Clinic visit X X X X X X X

CEA¹

Liver ultrasound

CT abdomen/pelvis X X X X X X X

Chest x-ray

CT chest X X X X X X X

4: CT

chest/abdomen/pelvis every 6 months for 2 years then annually with CEA every 3 months for 2 years then every 6 months for 3 years

Liver ultrasound

Chest x-ray

(4)

Other strategies

5: CEA every 6 months Clinic visit X X X X X X X X X X

CEA¹ X X X X X X X X X X

Liver ultrasound CT abdomen/pelvis Chest x-ray CT chest 6: Liver ultrasound

and chest x-ray every 6 months with CEA every 3 months for 2 years then every 6 months for 3 years

Liver ultrasound X X X X X X X X X X

CT abdomen/pelvis

Chest x-ray X X X X X X X X X X

CT chest 7: Liver ultrasound

and chest x-ray every 6 months with CEA every 6 months

Clinic visit X X X X X X X X X X

CT abdomen/pelvis

and chest x-ray annually with CEA every 3 months for 2 years then every 6 months for 3 years

Liver ultrasound X X X X X

CT abdomen/pelvis

Chest x-ray X X X X X

and chest x-ray annually with CEA every 6 months

CT abdomen/pelvis

(5)

and chest x-ray every 6 months for 2 years then annually with CEA every 3 months for 2 years then every 6 months for 3 years

Liver ultrasound X X X X X X X

CT abdomen/pelvis

Chest x-ray X X X X X X X

and chest x-ray every 6 months for 2 years then annually with CEA every 6 months

CT abdomen/pelvis

CT chest 12: CT

chest/abdomen/pelvis every 6 months with CEA every 3 months for 2 years then every 6 months for 3 years

Liver ultrasound

CT abdomen/pelvis X X X X X X X X X X

Chest x-ray

CT chest X X X X X X X X X X

13: CT

chest/abdomen/pelvis every 6 months with CEA every 6 months

Liver ultrasound

Chest x-ray

14: CT

chest/abdomen/pelvis annually with CEA every 3 months for 2 years then every 6 months for 3 years

Liver ultrasound

CT abdomen/pelvis X X X X X

Chest x-ray

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CT chest X X X X X 15: CT

chest/abdomen/pelvis annually with CEA every 6 months

Liver ultrasound

Chest x-ray

CT chest X X X X X

16: CT

chest/abdomen/pelvis every 6 months for 2 years then annually with CEA every 6 months

Liver ultrasound

Chest x-ray

17: Liver ultrasound and chest x-ray every 6 months

CEA¹

CT abdomen/pelvis

and chest x-ray annually

CEA¹

CT abdomen/pelvis

and chest x-ray every 6 months for 2 years then annually

Clinic visit X X X X X X X

CEA¹

CT abdomen/pelvis

(7)

CT chest 20: CT

chest/abdomen/pelvis every 6 months

CEA¹

Liver ultrasound

Chest x-ray

21: CT

chest/abdomen/pelvis annually

CEA¹

Liver ultrasound

Chest x-ray

CT chest X X X X X

22: CT

chest/abdomen/pelvis and CEA at 12 and 36 months

CEA¹ X X

Liver ultrasound

CT abdomen/pelvis X X

Chest x-ray

CT chest X X

23: CT

chest/abdomen/pelvis at 12 and 36 months

CEA¹

Liver ultrasound

CT abdomen/pelvis X X

Chest x-ray

CT chest X X

1Serum carcinoembryonic antigen

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Supplement Table 2: Effectiveness, cost, and incremental cost-effectiveness ratio for each surveillance strategy for individuals with a history of stage I colon cancer

Strategy Cost ($) Effectiveness (QALY¹) ICER²($/QALY)

Symptom Based Follow Up 8254 8.2138 0

CT³ chest/abdomen/pelvis at 1 year and 3 years 9897 8.2258 ---

Liver ultrasound and chest x-ray annually 9956 8.2317 94789

CEA⁴ and CT chest/abdomen/pelvis at 1 year and 3 years 10036 8.2267 ---

Liver ultrasound and chest x-ray every 6 months for 2 years then annually 11592 8.2387 ---

CT chest/abdomen/pelvis annually 12037 8.2404 ---

CEA every 6 months 12570 8.2458 ---

Liver ultrasound and chest x-ray annually with CEA every 6 months 13548 8.2512 184883

Liver ultrasound and chest x-ray every 6 months 13776 8.2488 ---

Liver ultrasound and chest x-ray every 6 months for 2 years then annually with CEA every 6 months 13957 8.2530 ---

CT chest/abdomen/pelvis every 6 months for 2 years then annually 14468 8.2481 ---

Liver ultrasound and chest x-ray every 6 months with CEA every 6 months 14508 8.2557 211340

CT chest/abdomen/pelvis annually with CEA every 6 months 15384 8.2540 ---

CEA every 3 months for 2 years then every 6 months for 3 years 15701 8.2544 ---

CT chest/abdomen/pelvis every 6 months for 2 years then annually with CEA every 6 months 16603 8.2566 ---

Liver ultrasound and chest x-ray annually with CEA every 3 months for 2 years then every 6 months

for 3 years 16660 8.2593 ---

Liver ultrasound and chest x-ray every 6 months for 2 years then annually with CEA every 3 months

for 2 years then every 6 months for 3 years 17049 8.2606 ---

Liver ultrasound and chest x-ray every 6 months with CEA every 3 months for 2 years then every 6

months for 3 years 17605 8.2634 403586

CT chest/abdomen/pelvis every 6 months 17661 8.2590 ---

CT chest/abdomen/pelvis every 6 months with CEA every 6 months 18191 8.2603 ---

CT chest/abdomen/pelvis annually with CEA every 3 months for 2 years then every 6 months for 3

years 18484 8.2618 ---

CT chest/abdomen/pelvis every 6 months for 2 years then annually with CEA every 3 months for 2

years then every 6 months for 3 years 19677 8.2637 ---

CT chest/abdomen/pelvis every 6 months with CEA every 3 months for 2 years then every 6 months

for 3 years 21273 8.2676 870194

1Quality-adjusted life years

2Incremental cost-effectiveness ratio

(9)

3Computed tomography

4Carcinoembryonic antigen

Strategies highlighted in red are less effective and more costly than another strategy, and strategies highlighted in yellow are less effective and most costly than a combination of 2 other strategies.

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Supplement Table 3: Effectiveness, cost, and incremental cost-effectiveness ratio for each surveillance strategy for individuals with a history of stage II colon cancer

Strategy Cost ($) Effectiveness (QALY¹) ICER²($/QALY)

CT³ chest/abdomen/pelvis at 1 year and 3 years 11649 7.8418 ---

CEA every 6 months 14789 7.8727 126275

Liver ultrasound and chest x-ray every 6 months for 2 years then annually with CEA every 6 months 16397 7.8847 ---

CT chest/abdomen/pelvis every 6 months for 2 years then annually with CEA every 6 months 19015 7.8906 ---

Liver ultrasound and chest x-ray annually with CEA every 3 months for 2 years then every 6 months for

3 years 19224 7.8940 ---

Liver ultrasound and chest x-ray every 6 months for 2 years then annually with CEA every 3 months for

2 years then every 6 months for 3 years 19667 7.8964 ---

Liver ultrasound and chest x-ray every 6 months with CEA every 3 months for 2 years then every 6

months for 3 years 20304 7.9009 279478

CT chest/abdomen/pelvis annually with CEA every 3 months for 2 years then every 6 months for 3

years 20998 7.8978 ---

CT chest/abdomen/pelvis every 6 months for 2 years then annually with CEA every 3 months for 2

CT chest/abdomen/pelvis every 6 months with CEA every 3 months for 2 years then every 6 months

for 3 years 23879 7.9076 529519

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Supplement Table 4: Effectiveness, cost, and incremental cost-effectiveness ratio for each surveillance strategy for individuals with a history of stage III colon cancer

Strategy Cost ($)

Effectiveness

(QALY¹) ICER²($/QALY)

CT³ chest/abdomen/pelvis at 1 year and 3 years 14905 6.4271 53300

CEA every 6 months 20950 6.5043 83463

Liver ultrasound and chest x-ray every 6 months for 2 years then annually with CEA every 6 months 23094 6.5279 95758

CT chest/abdomen/pelvis every 6 months for 2 years then annually with CEA every 6 months 25655 6.5394 --- Liver ultrasound and chest x-ray annually with CEA every 3 months for 2 years then every 6 months for 3

years 26355 6.5476 ---

Liver ultrasound and chest x-ray every 6 months for 2 years then annually with CEA every 3 months for 2

Liver ultrasound and chest x-ray every 6 months with CEA every 3 months for 2 years then every 6 months

for 3 years 27744 6.5608 155034

CT chest/abdomen/pelvis annually with CEA every 3 months for 2 years then every 6 months for 3 years 28027 6.5547 --- CT chest/abdomen/pelvis every 6 months for 2 years then annually with CEA every 3 months for 2 years then

every 6 months for 3 years 29425 6.5621 ---

CT chest/abdomen/pelvis every 6 months with CEA every 3 months for 2 years then every 6 months for 3

years 31120 6.5736 263847

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Supplement Table 5: Optimal surveillance strategy at willingness to pay thresholds of $50,000 to $200,000 for patients with a history of stage I to III colon cancer using hazard rate of death for patients with unresectable metastases which was derived from the median survival of patients receiving FOLFOXIRI and bevacizumab ⁶⁵

Willingness to pay threshold

$50,000/QALY¹ $100,000/QALY $150,000/QALY $200,000/QALY

Stage I Symptom-based follow-

up

Liver ultrasound and chest x-ray annually

liver ultrasound and chest x-ray annually with CEA every 6 months

Stage II Symptom-based follow-

up

Liver ultrasound and chest x-ray annually

Liver ultrasound and chest x-ray every 6 months with CEA every 6 months

Stage III Symptom-based follow-

up

Liver ultrasound and chest x-ray every 6 months with CEA² every 6 months

Liver ultrasound and chest x-ray every 6 months with CEA every 3 months for 2 years then every 6 months for 3 years³

Liver ultrasound and chest x-ray every 6 months with CEA every 3 months for 2 years then every 6 months for 3 years

1Quality adjusted life year

3Only the optimal strategy for stage III patients at a willingness to pay threshold of $150,000/QALY varied in this secondary analysis, compared to the base case

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Supplement Table 6: Strategies optimal in ≥10% of probabilistic sensitivity analysis iterations at a willingness to pay threshold of $100,000/QALY Surveillance strategy (% iterations optimal)

Stage I Symptom-based follow-up (43%)

Liver ultrasound and chest x-ray annually (40%) CEA every 6 months (13%)

Stage II Symptom-based follow-up (31%)

Liver ultrasound and chest x-ray annually (27%) CEA every 6 months (20%)

Stage III Liver ultrasound and chest x-ray every 6 months with CEA every 6 months (23%) Symptom-based follow-up (22%)

CEA every 6 months (14%)

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Supplement Figure 1a: Model predicted cumulative incidence of recurrence at 5 years compared to estimates from a population-based cohort study ^31,32

(17)

Supplement Figure 1b: Model predicted cumulative incidence of recurrence at 10 years compared to estimates from a population-based cohort study ^31,32

(18)

Supplement Figure 2a: Model predicted proportion of patients who undergo surgical treatment of recurrence compared to estimates from a randomized trial of intensive versus minimal surveillance strategies ⁶

(19)

Supplement Figure 2b: Model predicted 5-year overall survival compared to estimates from a population-based cohort study with median patient age of 71 years ⁶³

(20)

Supplement Figure 3a: Two-way sensitivity analysis displaying the optimal surveillance strategy at a willingness to pay threshold of (i)

$100,000/QALY and (ii) $200,000/QALY while varying the sensitivity and specificity of carcinoembryonic antigen testing for patients with a history of stage I colon cancer. Legend: Supplementary Figure 3d.

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Supplement Figure 3b: Two-way sensitivity analysis displaying the optimal surveillance strategy at a willingness to pay threshold of (i)

$100,000/QALY and (ii) $200,000/QALY while varying the sensitivity and specificity of carcinoembryonic antigen testing for patients with a history of stage II colon cancer. Legend: Supplementary Figure 3d.

(22)

Supplement Figure 3c: Two-way sensitivity analysis displaying the optimal surveillance strategy at a willingness to pay threshold of (i)

$100,000/QALY and (ii) $200,000/QALY while varying the sensitivity and specificity of carcinoembryonic antigen testing for patients with a history of stage III colon cancer. Legend: Supplementary Figure 3d.

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Supplement Figure 3d: Legend for Supplementary Figure 3

Strategy Colo

r Liver Ultrasound and Chest X Ray Annually

Liver ultrasound and chest x-ray every 6 months with CEA every 6 months Liver ultrasound and chest x-ray every 6 months with CEA every 3 months for 2 years then every 6 months for 3 years

CEA every 6 months

Liver ultrasound and chest x ray annually with CEA every 6 months

Liver ultrasound and chest x-ray every 6 months for 2 years then annually with CEA every 6 months