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. 2018 Sep 21;22(3):456–462. doi: 10.1007/s10120-018-0877-z

How long should we continue gastric cancer screening? From an epidemiological point of view

Yuri Mizota 1,✉, Seiichiro Yamamoto 1
PMCID: PMC6476823  PMID: 30242605

Abstract

Background

In Japan, incidence of gastric cancer is expected to follow the current downward trend as the younger generation has lower incidence of Helicobacter pylori infection. In this study we aimed to estimate how long gastric cancer screening is deemed necessary in the future from epidemiologic perspectives.

Methods

Following the Japanese guidelines for gastric cancer screening 2014, recommendation of providing population-based gastric cancer screening is judged by balancing benefits and harms. Benefits and harms are estimated by number needed to screen (NNS) < 1000 and Number Needed to Recall (NNR) < 100. NNS is the number of people required to participate in a screening to prevent one death and NNR is the number of people required to undergo diagnostic examination to prevent one death. These index are estimated for 2020–2035 using future projections of gastric cancer mortality for the scenarios of relative risk (RR) of 0.5–0.9 for mortality reduction by the screening.

Results

The criteria of both NNS < 1000 and NNR < 100 are fulfilled for the following age groups: when RR is set as 0.6, men ≥ 55 and women ≥ 65; when RR is set as 0.7 and 0.8, men ≥ 65 and women ≥ 75; when RR is set as 0.9, men ≥ 75 only.

Conclusions

In case of RR of 0.5 and 0.6, the gastric cancer screening are recommended for men ≥ 55 and women ≥ 65 until 2035, while it is not recommended for men and women in the 45–54 even in 2010 and 2015.

Keywords: Gastric cancer, Cancer screening, Guidelines

Introduction

In Japan, incidence of gastric cancer is expected to follow the current downward trend as the younger generation has lower incidence of Helicobacter pylori infection [1]. In this study, therefore, we aimed to estimate how long gastric cancer screening is deemed necessary in the future from epidemiologic and statistical perspectives. Of note, for clarification purposes, population-based screening was selected as a screening mode to be analyzed in this study.

In Japan, based on the “Japanese guidelines for gastric cancer screening 2014 edition” edited by the National Cancer Center [2], the Ministry of Health, Labor, and Welfare recommends radiographic screening and endoscopy as population-based screening [3]. Especially, endoscopy screening was recommended very recently since 2016. In principle, population-based screening should be introduced and conducted after comparing and weighing the benefits regarding mortality reduction and harms concerning screening [4, 5]. Even though there are many disagreements over whether performing screenings falling short of such standard is justifiable, few may take a critical attitude toward conducting screenings if they meet this standard. The challenge here is how to compare the benefits, i.e., size of mortality reduction, to the potential harms of screening. The most common harms associated with screening include false-negative test results, false-positive test results, overdiagnosis, as well as adverse reactions to screening and diagnostic examination procedures. It is not easy to compare these issues with the size of mortality reduction effect because they have fundamentally different natures. In the Japanese guidelines for cancer screening 2014 edition, for comparison between benefits and harms of screening, Number Needed to Screen (NNS), representing the size of mortality reduction effect, is used as a benefit indicator, while recall rate is employed as a risk indicator, which is the same as the Japanese guidelines for breast cancer screening [6]. NNS is an estimated number of people required to participate in a screening program to prevent one death over a defined time interval, and thus the smaller NNS implies larger benefits. On the other hand, recall rate is the number of people required to undergo diagnostic examination procedures to prevent one death over a defined time interval, referred as number needed to recall (NNR) in this article, and the larger NNR implies larger harms, i.e., causing inconvenience to more people. In the above-mentioned Guidelines, the thresholds of 1000 and 100 are set as tentative criteria for NNS and NNR, respectively. To judge the length to continue gastric cancer screening, these criteria were used in the present study due to the following facts: these numbers have been employed in the Guidelines in widespread use; using them can allow qualitative analyses; and there are no alternative proven criteria available. In short, we calculate NNS and NNR, compare them to their corresponding threshold of 1000 and 100, and use the comparison results as a part of a basis for deciding whether it is justifiable to continue or discontinue the gastric cancer screening programs.

To maximize the effect of population-based screening, higher participation rate is necessary. Nevertheless, participation rate is as low as 40% in Japan [7] and the government set the goal as 50% in the Third term Basic Plan to Promote Cancer Control Programs in Japan [8]. Since the number of life saved (NLS) varies according to the participation rate, NLS of participation rate 50% and 100% compared to that of NLS of present rate (40%) are also used as a benefit indicator in this study.

Methods

NNS, NNR, and NLS are estimated by sex and age group. Estimations of NNS, NNR, and NLS require data on gastric cancer mortality, screening effect on mortality reduction, and recall rate. The projections of future gastric cancer deaths by sex and age group in Japan are available from the National Cancer Center [9]. While people are divided into the 7 age groups as follows: 0–14, 15–44, 45–54, 55–64, 65–74, older than or equal to 75 years of age, and all ages, we selected age groups at the time of screening as follows: 45–54, 55–64, 65–74, and older than or equal to 75 years of age in our study. In addition to the number of deaths, estimations of mortality rates require estimates of future population, which should be calculated using the same method and numbers used for calculation of the number of deaths, and thus, we used the method described in the reference [10]. However, since there is no publicly disclosed prediction for the future Japanese population in the period of 2015 and beyond, a ratio of Japanese population to the total population in Japan by sex and 5-year age groups were calculated, which in turn was multiplied by the total population estimates (estimated median numbers of births and deaths) for the year of 2020, 2025, 2030, and 2035, to obtain estimates of future Japanese population by sex and 5-year age groups. These data on the Japanese total population are published by The National Institute of Population and Social Security Research [11]. The projections of the gastric cancer mortality rates are estimated for 2020, 2025, 2030, and 2035 using future number of deaths estimates of 2020–2024, 2025–2029, 2030–2034, and 2035–2039, respectively. Mortality trends are shown using observed value until 2015 [12] and estimates for 2020–2035.

To estimate NNS, the above-mentioned Guidelines used relative risks (RR) of gastric cancer mortality reduction for effectiveness of radiography test and endoscopy test from several studies [13–15]. In this study, several relative risk values associated with screening are used for estimation of future NNSs and NNRs in different scenarios. For reference, Table 1 lists the relative risk values used in the Guidelines. These relative risk values ranged from 0.1 to 1.07, which included those either too large or too small to exert any effects, and thus 5 values (0.5, 0.6, 0.7, 0.8, and 0.9) were selected to be used in the scenarios in this study. Recently Korean study reported that the effectiveness of endoscopy screening is RR of 0.53 (95% CI 0.51–0.56), which is not contradict from our scenarios [16].

Table 1.

Relative risk used to estimate number needed to screen in the Japanese guidelines for gastric cancer

Screening Study Sex Age-specific relative risk
40 45 50 55 60 65 70 75
Radiography Abe et al. [13] Male 0.105 0.105 0.25 0.25 0.271 0.271 0.429 0.429
Female 0.778 0.778 0.2 0.2 0.385 0.385 0.882 0.882
Fukao et al. [14] Male 0.46 0.46 0.34 0.34 0.25 0.25
Female 1.07 1.07 0.45 0.45 0.63 0.63
Hamashima et al. [15] Male 0.865 0.865 0.865 0.865 0.865 0.865 0.865 0.865
Female 0.865 0.865 0.865 0.865 0.865 0.865 0.865 0.865
Endoscopy Hamashima et al. [15] Male 0.695 0.695 0.695 0.695 0.695 0.695 0.695 0.695
Female 0.695 0.695 0.695 0.695 0.695 0.695 0.695 0.695
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Japanese Guidelines for Gastric Cancer 2014 edition. http://canscreen.ncc.go.jp/

Recall rates cited in the above-mentioned Guidelines are radiography test data derived from the annual report 2011 of The Japanese Society of Gastrointestinal Cancer Screening [17], and endoscopy data collected in Niigata City reported in 2012 [18] (Table 2). The ranges of recall rates for radiography test and endoscopy were reported as 4.1–12.2% and 2.9–11.6%, respectively. In this study, we used relative risks of 5% and 10% as scenarios.

Table 2.

Recall rate used to estimate number needed to recall in the Japanese guidelines for gastric cancer

Screening Study Sex Age-specific recall rate (%)
40 45 50 55 60 65 70 75
Radiography JSGCS [17] Male 4.8 6.0 7.9 9.8 11.3 11.9 12.2 12.2
Female 4.1 4.72 5.7 6.5 7.3 7.9 8.5 8.5
Endoscopy Niigata City [18] Male 2.9 8.9 11.6 9.7 11.5 11.0 11.2 11.2
Female 5.8 5.4 6.4 6.7 7.5 7.3 7.3 7.3
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Japanese Guidelines for Gastric Cancer 2014 edition. http://canscreen.ncc.go.jp/

For estimating NLS, hypothetical number of gastric cancer deaths without screening, D0s, is estimated as follows:

D^0=Dobs1-Pobs1-RR,

where Dobs is observed number of deaths and Pobs is observed participation rate of screening. NLSt is estimated as a function of target participation rate Pt:

NL^St=D01-Pt1-RR.

The observed participation rate is set as 40% and target participation rates are set as 50% and 100%. For the future predication, Pobs is assumed as the same as the present participation rate, i.e., 40%.

Results

Figures 1 and 2 show past transition and future projections of gastric cancer mortalities by age groups. Downward trends are obvious for both men and women in every age group equal to and older than 45 years old.

Fig. 1.

Fig. 1

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Observed and projected trends of age-specific gastric cancer mortality in Japan for male

Fig. 2.

Fig. 2

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Observed and projected trends of age-specific gastric cancer mortality in Japan for female

Tables 3 and 4 show estimates of NNS and NNR. It might be obvious, but higher relative risks (small effect) and/or lower mortality rates make NNS higher. The results indicated that the benefits of the screening exceeded harms more prominently in men than women, older than younger age groups, and now than future. The criteria of both NNS and NNR would be fulfilled, that is, the both benefits and harms are considered within acceptable limits to justify the screening, for the following age groups (year-old): when relative risk (RR) of screening is set as 0.5, men ≥ 55 and women ≥ 65; when RR is set as 0.6, men ≥ 55 and women ≥ 65; when RR is set as 0.7, men ≥ 65 and women ≥ 75; and when RR is set as 0.8, men ≥ 65 and women ≥ 75; when RR is set as 0.9, men ≥ 75 only.

Table 3.

Number needed to screen, number needed to recall, and number of life saved by gastric cancer screening based on future prediction of gastric cancer mortality

Mortality reductiona Year Age 45–54 Age 55–64 Age 65–74 Age 75-
Mortality rate for 10 yearsb (%) NNSc NNRd NLS5 Mortality rate for 10 years (%) NNS NNR NLS Mortality rate for 10 years (%) NNS NNR NLS Mortality rate for 10 years (%) NNS NNR NLS
Recall rate Participation rate Recall rate Participation rate Recall rate Participation rate Recall rate Participation rate
5% 10% 50% 100% 5% 10% 50% 100% 5% 10% 50% 100% 5% 10% 50% 100%
RRd = 0.5 2010 0.13 1560 78 156 63 376 0.54 372 19 37 310 1861 1.32 151 8 15 593 3559 3.21 62 3 6 1071 6428
2015 0.09 2140 107 214 49 293 0.40 497 25 50 199 1197 1.09 184 9 18 565 3393 2.79 72 4 7 1095 6572
2020 0.07 2709 135 271 43 255 0.31 643 32 64 147 881 0.93 214 11 21 486 2914 2.54 79 4 8 1165 6990
2025 0.10 2725 136 273 41 248 0.33 706 35 71 143 855 0.89 252 13 25 354 2126 2.55 89 4 9 1229 7376
2030 0.08 2503 125 250 39 233 0.28 725 36 73 153 919 0.72 278 14 28 308 1849 2.13 94 5 9 1224 7346
2035 0.09 2210 110 221 39 233 0.27 732 37 73 148 889 0.69 290 14 29 317 1901 2.04 98 5 10 1148 6885
RR = 0.6 2010 0.13 1950 97 195 48 287 0.54 465 23 47 236 1418 1.32 189 9 19 452 2711 3.21 78 4 8 816 4897
2015 0.09 2675 134 268 37 223 0.40 621 31 62 152 912 1.09 230 11 23 431 2585 2.79 90 4 9 835 5007
2020 0.07 3386 169 339 32 194 0.31 804 40 80 112 671 0.93 268 13 27 370 2220 2.54 98 5 10 888 5326
2025 0.10 3407 170 341 31 189 0.33 882 44 88 109 651 0.89 315 16 32 270 1620 2.55 111 6 11 937 5620
2030 0.08 3129 156 313 30 177 0.28 906 45 91 117 700 0.72 348 17 35 235 1409 2.13 117 6 12 933 5597
2035 0.09 2762 138 276 30 177 0.27 915 46 92 113 677 0.69 362 18 36 241 1449 2.04 123 6 12 874 5246
RR = 0.7 2010 0.13 2600 130 260 34 205 0.54 620 31 62 169 1015 1.32 252 13 25 324 1941 3.21 104 5 10 584 3506
2015 0.09 3567 178 357 27 160 0.40 829 41 83 109 653 1.09 306 15 31 308 1851 2.79 120 6 12 597 3585
2020 0.07 4515 226 452 23 139 0.31 1072 54 107 80 481 0.93 357 18 36 265 1589 2.54 131 7 13 635 3813
2025 0.10 4542 227 454 23 135 0.33 1176 59 118 78 466 0.89 420 21 42 193 1160 2.55 148 7 15 671 4023
2030 0.08 4171 209 417 21 127 0.28 1208 60 121 84 501 0.72 463 23 46 168 1008 2.13 156 8 16 668 4007
2035 0.09 3683 184 368 21 127 0.27 1220 61 122 81 485 0.69 483 24 48 173 1037 2.04 163 8 16 626 3755
RR = 0.8 2010 0.13 3900 195 390 22 131 0.54 930 47 93 108 647 1.32 378 19 38 206 1238 3.21 156 8 16 373 2236
2015 0.09 5351 268 535 17 102 0.40 1243 62 124 69 416 1.09 459 23 46 197 1180 2.79 179 9 18 381 2286
2020 0.07 6773 339 677 15 89 0.31 1608 80 161 51 307 0.93 535 27 54 169 1013 2.54 197 10 20 405 2431
2025 0.10 6814 341 681 14 86 0.33 1765 88 176 50 297 0.89 630 32 63 123 740 2.55 222 11 22 428 2566
2030 0.08 6257 313 626 13 81 0.28 1813 91 181 53 320 0.72 695 35 70 107 643 2.13 234 12 23 426 2555
2035 0.09 5525 276 552 13 81 0.27 1830 92 183 52 309 0.69 724 36 72 110 661 2.04 245 12 25 399 2395
RR = 0.9 2010 0.13 7799 390 780 10 63 0.54 1860 93 186 52 310 1.32 755 38 76 99 593 3.21 312 16 31 179 1071
2015 0.09 10702 535 1070 8 49 0.40 2486 124 249 33 199 1.09 918 46 92 94 565 2.79 359 18 36 183 1095
2020 0.07 13546 677 1355 7 43 0.31 3215 161 322 24 147 0.93 1071 54 107 81 486 2.54 394 20 39 194 1165
2025 0.10 13627 681 1363 7 41 0.33 3529 176 353 24 143 0.89 1261 63 126 59 354 2.55 444 22 44 205 1229
2030 0.08 12514 626 1251 6 39 0.28 3625 181 363 26 153 0.72 1390 70 139 51 308 2.13 469 23 47 204 1224
2035 0.09 11050 552 1105 6 39 0.27 3661 183 366 25 148 0.69 1448 72 145 53 317 2.04 490 25 49 191 1148
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aRelative risk for mortality reduction by screening

bGastric cancer mortality rate fro 10 years

cNumber needed to screen

dNumber needed to recall

eNumber of life saved

Table 4.

Number needed to screen, number needed to recall, and number of life saved by gastric cancer screening based on future prediction of gastric cancer mortality

Mortality reductiona Year Age 45–54 Age 55–64 Age 65–74 Age 75-
Mortality rate for 10 yearsb (%) NNSc NNRd NLSe Mortality rate for 10 years (%) NNS NNR NLS Mortality rate for 10 years (%) NNS NNR NLS Mortality rate for 10 years (%) NNS NNR NLS
Recall rate Participation rate Recall rate Participation rate Recall rate Participation rate Recall rate Participation rate
5% 10% 50% 100% 5% 10% 50% 100% 5% 10% 50% 100% 5% 10% 50% 100%
RR = 0.5 2010 0.08 2497 125 250 39 233 0.20 1019 51 102 116 698 0.38 525 26 53 192 1149 1.28 156 8 16 706 4236
2015 0.06 3339 167 334 31 184 0.15 1304 65 130 77 465 0.32 617 31 62 186 1113 1.09 183 9 18 680 4081
2020 0.04 4893 245 489 23 139 0.12 1722 86 172 56 334 0.30 675 34 68 168 1009 0.98 204 10 20 694 4166
2025 0.04 5198 260 520 21 128 0.10 1980 99 198 51 308 0.25 792 40 79 123 735 0.91 221 11 22 736 4418
2030 0.04 5090 255 509 19 113 0.09 2124 106 212 53 315 0.23 887 44 89 104 623 0.90 222 11 22 768 4609
2035 0.04 4791 240 479 18 105 0.09 2234 112 223 49 293 0.21 959 48 96 102 611 0.92 218 11 22 775 4650
RR = 0.6 2010 0.08 3121 156 312 30 177 0.20 1273 64 127 89 532 0.38 656 33 66 146 876 1.28 195 10 19 538 3227
2015 0.06 4174 209 417 23 140 0.15 1630 82 163 59 354 0.32 771 39 77 141 848 1.09 229 11 23 518 3109
2020 0.04 6117 306 612 18 106 0.12 2153 108 215 42 254 0.30 844 42 84 128 769 0.98 255 13 25 529 3174
2025 0.04 6497 325 650 16 97 0.10 2475 124 247 39 234 0.25 990 50 99 93 560 0.91 276 14 28 561 3366
2030 0.04 6363 318 636 14 86 0.09 2655 133 266 40 240 0.23 1109 55 111 79 474 0.90 277 14 28 585 3511
2035 0.04 5989 299 599 13 80 0.09 2792 140 279 37 223 0.21 1199 60 120 78 466 0.92 273 14 27 590 3543
RR = 0.7 2010 0.08 4161 208 416 21 127 0.20 1698 85 170 63 381 0.38 875 44 88 104 627 1.28 260 13 26 385 2311
2015 0.06 5565 278 557 17 100 0.15 2173 109 217 42 253 0.32 1028 51 103 101 607 1.09 306 15 31 371 2226
2020 0.04 8156 408 816 13 76 0.12 2870 144 287 30 182 0.30 1125 56 113 92 550 0.98 339 17 34 379 2273
2025 0.04 8663 433 866 12 70 0.10 3300 165 330 28 168 0.25 1320 59 132 67 401 0.91 368 18 37 402 2410
2030 0.04 8484 424 848 10 61 0.09 3541 177 354 29 172 0.23 1478 74 148 57 340 0.90 370 18 37 419 2514
2035 0.04 7985 399 799 10 57 0.09 3723 186 372 27 160 0.21 1599 80 160 56 333 0.92 363 18 36 423 2536
RR = 0.8 2010 0.08 6241 312 624 14 81 0.20 2546 127 255 40 243 0.38 1313 66 131 67 400 1.28 390 19 39 246 1473
2015 0.06 8348 417 835 11 64 0.15 3260 163 326 27 162 0.32 1542 77 154 65 387 1.09 459 23 46 237 1420
2020 0.04 12234 612 1223 8 48 0.12 4306 215 431 19 116 0.30 1688 84 169 58 351 0.98 509 25 51 242 1449
2025 0.04 12994 650 1299 7 44 0.10 4949 247 495 18 107 0.25 1980 99 198 43 256 0.91 551 28 55 256 1537
2030 0.04 12726 636 1273 7 39 0.09 5311 266 531 18 110 0.23 2218 111 222 36 217 0.90 554 28 55 267 1603
2035 0.04 11978 599 1198 6 37 0.09 5584 279 558 17 102 0.21 2398 120 240 35 213 0.92 545 27 55 270 1617
RR = 0.9 2010 0.08 12483 624 1248 6 39 0.20 5093 255 509 19 116 0.38 2626 131 263 32 192 1.28 779 39 78 118 706
2015 0.06 16695 835 1670 5 31 0.15 6520 326 652 13 77 0.32 3083 154 308 31 186 1.09 917 46 92 113 680
2020 0.04 24467 1223 2447 4 23 0.12 8611 431 861 9 56 0.30 3376 169 338 28 168 0.98 1018 51 102 116 694
2025 0.04 25988 1299 2599 4 21 0.10 9899 495 990 9 51 0.25 3960 198 396 20 123 0.91 1103 55 110 123 736
2030 0.04 25452 1273 2545 3 19 0.09 10622 531 1062 9 53 0.23 4435 222 444 17 104 0.90 1109 55 111 128 768
2035 0.04 23955 1198 2396 3 18 0.09 11169 558 1117 8 49 0.21 4796 240 480 17 102 0.92 1090 55 109 129 775
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aRelative risk for mortality reduction by screening

bGastric cancer mortality rate fro 10 years

cNumber needed to screen

dNumber needed to recall

eNumber of life saved

NLS, which is a function of RR, mortality, and participation rate, is substantial for age 65 or older when participation rate is 50% as a national goal while it is not so large for either two combination of female, RR ≥ 0.8, and age 54 or younger.

Discussion

In this study, target population and length appropriate to continue gastric cancer screening were investigated based on the future projection of gastric cancer mortality, from the standpoint of balancing the benefits and harms of the screening. As a result, until 2035, screening programs with higher mortality reduction effects (relative risk 0.5 and 0.6) are shown to be beneficial for men ≥ age 55 and women ≥ age 65. It is expected that, under conditions and scenarios selected in this study, both men and women in the 45–54 age group did not meet the criteria for benefits and harms even in 2010 and 2015.

This study can provide evidence for the decision based on benefits and harms by numerical criteria using NNS, NNR, and NSL. In this way, balancing estimates of benefits and harms is a standard method to evaluate whether to introduce and continue population-based screening [5, 19, 20]. While more comprehensive balance sheets have been proposed [21, 22], typical indicators are those for concerning mortality reduction for benefit and false-positive, overdiagnosis, and adverse reactions to screening and diagnostic examination procedures for harm [19, 20, 23]. The NNS and NNR used in this study are transformed indictors of mortality reduction and false-positive for intuitive interpretation. Overdiagnosis indicators cannot be examined due to lack of reports about overdiagnosis for gastric cancer screening [2]. Because of the difficulty of comparing severity of adverse reactions with screening benefit in numerical way, NNS and NNR were used to balance benefits and harms in this study. As for the threshold, no consensus was obtained due to the uncertainty and variability in the evidence used to make these estimates [20] or a matter of individual judgement [19]. In this study, we used threshold of 1000 for NNS and 100 for NNR based on the Japanese guidelines for cancer screening 2014 edition [2]. These threshold has some sense in Japan because the recommendation of the guideline and following government decision was made based on this value. Even in case of not using such threshold, combination of NNS and NNR for various scenarios in Tables 3 and 4 will help to evaluate whether to continue gastric cancer screening.

There are several limitations in this study. NNSs, NNRs, and NLS addressed in this study are limited to those estimated using the data obtained for both male and female in the age groups of 45–54, 55–64, 65–74, and equal to and older than 75 years, projected for 2020, 2025, 2030, and 2035, due to limited availability of the relevant data. The accurate data of the effect size of screening on mortality, recall rate, and participation rate are not available in Japan, while the detailed and accurate data on mortality rates and their projections were available. Unfortunately, however, although stomach cancer screening has been recommended for age 40 or older until 2015 and is recommended for age 50 or older since 2016, the projections are only available for age groups of 45–54, 55–64, 65–74, and equal to and older than 75 years old. Although NNSs, NNRs, and NLSs outside of these scenarios cannot be estimated due to data availability, they can be speculated by intrapolation of the values of mortality rate, relative risk, and recall rate within the scenarios. Owing to the simple relationships among these values, the results can be speculated that gastric cancer screening is not recommended for men and women with age 50 based on the threshold of NNS < 1000 and NNR > 100 for all the scenarios (Tables 3, 4). As a matter of course, in real situations, other benefits and harms of the screening should be considered such as less invasive treatment due to early detection as benefits and adverse reactions of the screening and diagnostic examinations as harms.

Considering the criteria of benefits and harms as NNS < 1000 and NNR > 100, respectively, these estimates may imply that, compared to sex, age and screening effect, the trend toward mortality reduction may have less impact on NNS and NNR, at least until 2035. Recall rates are closely related to prevalence, sensitivity, specificity, and screening effect, and therefore, it is important to manage the accuracy level of screening to maintain the recall rates in reasonable range. Furthermore, NLS heavily depends on participation rate of screening, it is most important to increase participation rate as high as possible.

Funding

This study was supported by the National Cancer Center Research and Developmental Fund (29-A-20).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical consideration

This article does not contain any studies with human or animal subjects performed by any of the authors.

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