There is evidence that cancer survivors are at increased risk of second primary cancers. Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks. Methods: We examined the incidence of second primary cancer among adults in the West of Scotland, UK, diagnosed with cancer between 2000 and 2004 (n = 57,393).
Coyte et al BMC Cancer 2014, 14:272 http://www.biomedcentral.com/1471-2407/14/272 RESEARCH ARTICLE Open Access Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study Aishah Coyte1, David S Morrison2 and Philip McLoone2* Abstract Background: There is evidence that cancer survivors are at increased risk of second primary cancers Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks Methods: We examined the incidence of second primary cancer among adults in the West of Scotland, UK, diagnosed with cancer between 2000 and 2004 (n = 57,393) We used National Cancer Institute Surveillance Epidemiology and End Results and International Agency for Research on Cancer definitions of multiple primary cancers and estimated indirectly standardised incidence ratios (SIR) with 95% confidence intervals (CI) Results: There was a high incidence of cancer during the first 60 days following diagnosis (SIR = 2.36, 95% CI = 2.12 to 2.63) When this period was excluded the risk was not raised, but it was high for some patient groups; in particular women aged 1 -5 years 1682 103464 1.6 0.8 0-5 years 2966 145435 2.0 1.0 *excluding non-melanoma skin cancer †age & sex standardised (European standard population ages 15 to 85+) years Figure shows the rates expressed as standardised incidence ratios (SIR) for men and women The risk in the first 60 days was times the population risk for women and times the risk for men Between 60 days and year risks were lower than the reference population The overall SIR between day-5 years was 1.07 (95%CI = 1.03 to 1.11) for both sexes combined The age, sex and 5-year survival of the 56,564 patients who did not have a cancer in the first 60 days is summarised in Table Forty seven percent were aged 70 and over, sixty one percent died within five years, and 2137 (3.8%) had a second primary cancer Table shows there was concordance in the order of first and second primary cancers Lung cancer comprised 19% and 24% of first and second cancers, respectively; colorectal cancer comprised 13% and 15%; and female breast cancer represented 15% and 11% Five year survival and the proportion of patients who had a further cancer were associated One to two percent of patients with cancers with poor survival (6-25% alive at years for lung, oesophagus, ovarian, and stomach cancer) had a further primary cancer The proportion of second cancers among patients with cancers with better survival (37-79% alive at years) ranged from 4% for colorectal to 8.5% for head & neck cancers Compared to the distribution of index cancers sites (Table 2), there were higher proportions of head & neck cancers (13% vs 4% of index cancers) among patients with lung cancer, higher proportions of lung cancer (43% vs 19%) among head & neck cancer patients, and higher proportions of prostate (28% vs 9%) and lung cancers (36% vs 19%) among patients with bladder cancer P < 0.0001 for each comparison Later cancers at the same site may be recurrences rather than true primaries Table shows the number of registered subsequent primary cancers, in the same ICD10 category as the index cancer, classified by IARC/IACR and SEER rules In each case SEER included a greater number of second primaries than IARC/IACR Female breast cancer showed the greatest difference; 79 of 98 Figure Standardised incidence ratios (SIR) for subsequent primary cancers Site of first primary cancer All cancer* (C00-C97) Lung (C33-34) Colorectal (C18-20) Female breast (C50) Prostate (C61) Head & neck Stomach (C00-14, C30-32) (C16) Bladder (C67) Oesophagus Melanoma (C15) (C43) Ovarian (C56) n n n n n n (%) n n n (%) n 2398 (4.2) 2079 (3.7) 1780 (3.1) 1696 (3.0) (70.8) 1262 (60.7) 1233 (67.3) 1094 (61.5) 736 (43.4) (12.2) 70.6 (11.6) 55.5 (18.0) 63.8 (%) (%) (%) Total 56564 Men 27561 (48.7) 5894 (54.8) 3834 (53.1) Mean age (SD) years 66.6 (13.8) 70.0 (10.2) 69.9 (11.7) 62.0 (11.3) 345 (3.2) (5.4) (%) (%) 10764 (19.0) 7225 (12.8) 8386 (14.8) 5269 (9.3) 5269 (100.0) 1697 (14.3) 71.6 (9.1) 63.3 (%) (%) 1832 (3.2) (11.7) 71.8 (10.5) 69.8 n (%) (%) 1325 (2.3) (14.7) Age (years) 15– < 50 6386 50– < 70 23787 (42.1) 4513 70+ 26391 (46.7) 5906 Number of patients with second 2137 primary cancer* (3.8) 119 388 1660 (19.8) 42 (0.8) (41.9) 2868 (39.7) 4089 (48.8) 2098 (39.8) 277 (11.6) 113 (5.4) 1385 (57.8) 763 (36.7) 658 46 (2.5) 85 (35.9) 735 (4.8) 646 (38.1) 219 (16.5) (41.3) 619 (36.5) 599 (45.2) (54.9) 3969 (54.9) 2637 (31.4) 3129 (59.4) 736 (30.7) 1203 (57.9) 1128 (61.6) 960 (53.9) 431 (25.4) 507 (38.3) (1.1) (6.5) 204 (8.5) 46 (2.2) (1.5) 102 (6.0) (1.5) 324 (4.5) 363 (4.3) 342 140 (7.6) 26 20 Coyte et al BMC Cancer 2014, 14:272 http://www.biomedcentral.com/1471-2407/14/272 Table Baseline characteristics and outcomes Second or later cancer Lung (C33-34) 507 (23.7) 24 (20.2) 65 (20.1) 67 (18.5) 91 (26.6) 88 (43.1) 13 (28.3) 50 (35.7) (23.1) 14 (13.7) (15.0) Colorectal (C18-20) 315 (14.7) 11 (9.2) (17.3) 52 (14.3) 80 (23.4) 17 (8.3) (17.4) 15 (10.7) (23.1) (8.8) (5.0) Female Breast (C50) 237 (11.1) 14 (11.8) 25 (7.7) (27.0) (0.0) (2.5) (13.0) (2.1) (0.0) 15 (14.7) Prostate (C61) (13.9) 56 45 98 (30.0) 162 (7.6) 11 (9.2) (0.0) (0.9) 11 (5.4) (6.5) 39 (27.9) (3.8) (7.8) (0.0) Head & neck (C00-C14, C30-C32) 107 (5.0) 15 (12.6) 12 (3.7) 11 (3.0) 15 (4.4) 32 (15.7) (4.3) (1.4) (19.2) (2.0) (0.0) Stomach (C16) 83 (3.9) (5.0) 16 (4.9) (1.9) 22 (6.4) (2.9) (6.5) (5.0) (0.0) (0.0) (0.0) Bladder (C67) 78 (3.6) (6.7) (2.8) (1.7) 20 (5.8) (4.4) (4.3) (0.7) (7.7) (2.9) (0.0) (0.0) Oesophagus (C15) 73 (3.4) (3.4) (2.2) (2.5) 10 (2.9) 18 (8.8) (2.2) (2.1) (3.8) (2.9) Melanoma (C43) 84 (3.9) (1.7) (2.5) 17 (4.7) 14 (4.1) (0.0) (2.2) (1.4) (0.0) 28 (27.5) Pancreas (C25) 49 (2.3) (0.8) 12 (3.7) 10 (2.8) (2.0) (0.5) (2.2) (3.6) (0.0) (3.9) (0.0) Ovarian (C56) 34 (1.6) (0.0) (0.9) 19 (5.2) (0.0) (0.0) (0.0) (0.0) (0.0) (1.0) (5.0) Kidney (C64) 52 (2.4) (5.0) (2.2) (1.9) (3.2) (2.0) (2.2) (0.0) (3.8) (2.0) (0.0) Corpus uteri (C54) 42 (2.0) (0.8) (2.8) 20 (5.5) (0.0) (1.0) (2.2) (0.0) (3.8) (0.0) (15.0) All other cancers* 314 (13.9) 16 (10.6) 69 (19.2) (8.5) 13 (8.8) Number of deaths 34648 (61.3) 10130 (94.1) 4283 (59.3) 2429 (29.0) 2169 (41.2) (14.7) 40 11 (4.8) 1262 (52.6) 1835 (88.3) 1157 (63.2) 1629 (11.1) 13 (11.9) (19.0) (91.5) 373 (22.0) 879 (66.3) Page of 11 *excluding non-melanoma skin cancer (12.9) 50 11 (10.0) Coyte et al BMC Cancer 2014, 14:272 http://www.biomedcentral.com/1471-2407/14/272 Page of 11 Table Number of same site second primary cancers Number of subsequent same site primary cancers‡ Registry IARC/IACR rules SEER rules First primary cancer n n n Lung (C33-34) 24 17 Colorectal (C18-20) 56 31 55 Female Breast (C50) 98 79 Prostate (C61) 0 24 29 Head & neck (C00-C14, C30-C32) 32 Stomach (C16) Bladder (C67) 1 Oesophagus (C15) 0 Melanoma (C43) 28 28 Pancreas (C25) 0 Ovarian (C56) 1 Kidney (C64) Corpus uteri (C54) 1 Abbreviations: SEER Surveillance Epidemiology and End Results, IARC International Agency for Research on Cancer, IACR International Association of Cancer Registries ‡diagnosed >60 days- years after first primary cancer subsequent breast cancers were classified as second primaries by SEER but only by IARC For malignant melanoma, all 28 subsequent melanomas were identified as second primaries by SEER but none by IARC/IACR rules There was a smaller difference for head & neck cancers, for which SEER and IARC/IACR included 29 and 24 of 32 subsequent head & neck cancers Table shows the relative risk of second primary cancers using all registrations, all registrations applying IARC/ IACR and SEER rules, and all registrations excluding same site cancers There was no overall difference in cancer incidence compared to the general population (SIR = 0.96, 95% CI = 0.91 to 1.00; SIR = 0.99, 95% CI = 0.94 to 1.04 excluding same site cancers) IARC/IACR rules, which excluded the largest number of subsequent cancers, suggested a lower risk (SIR = 0.86, 95% CI = 0.81 to 0.90) Patients with lung, colorectal, breast (aged ≥50 years), prostate and ovarian cancers were at lower risk of further cancers compared with the general population IARC/ IACR and SEER rules reduced the estimated risks further Patients with cancers of the head & neck, bladder, and breast (women aged