Among 2,29,554 BCa survivors, 16.6% had SPCs and 13.8% had second primary cancers (83.0% male; 91.5% white; and 62.5% died. For SPCs, median age at diagnosis was 74 years (67–81), and median follow-up was 82 months (38–132) (eTable1).

Among BCa survivors, 38,207 had SPCs and 17,546 died from SPCs (Figs. 1 and 4). Among male survivors, 31,836 had SPC and 13,895 died from it (Table 1). The most common SPCs were prostate (35.2%), lung (19.5%), and colorectal (7.0%). The most common SPC causes of death were lung (31.6%), prostate (8.4%), and colorectal (5.5%). Among female survivors, 6,371 had SPC and 3,651 died from it (Table 1). The top SPCs were lung (28.0%), breast (19.0%), and colorectal (8.3%). The top SPC causes of death were lung (31.4%), kidney and renal pelvis (5.8%), and pancreas (5.1%). Additionally, the proportion of SPCs varied by sex in patient age group, calendar year, and during follow-up (Figs. 1 and 4).

The proportion of new subsequent primary cancers among bladder cancer survivors by sex (A, B, C),

The risk of developing SPCs was 57% higher among BCa survivors than general population [SIR, 1.57 (95%CI, 1.56–1.59)] in men, and SIR of SPCs, except melanoma and lymphoma, of the 12 common SPCs were significantly higher. The greatest SIR was in ureters [14.06 (95%CI, 12.99–15.19)], kidney and renal pelvis [2.06 (95%CI, 2.27–4.75)], prostate [2.07 (95%CI, 2.03–2.11)], and lung [1.86 (95%CI, 1.81–1.91)]. SIRs of ureters, kidney and renal pelvis, and lung decreased with age in men and prolongation of diagnosis. SIR of prostate is relatively stable in different age groups and decreased as prolongation of diagnosis, but was higher than that of the general population, except for SIR of prostate > 5 years after diagnosis. Since 2000, SIR of ureters gradually decreased, of prostate and lung gradually increased, while that of kidney and renal pelvis is relatively stable. In women, the risk of developing SPCs was 39% higher than general population[SIR, 1.39 (95%CI, 1.36–1.42)], and SIR of 6 of the 14 common SPCs were significantly higher. The greatest SIR was in ureters [SIR, 25.27 (95%CI, 21.65–29.32)], kidney and renal pelvis [SIR, 3.55 (95%CI, 3.22–3.90)], lung [SIR, 2.40 (95%CI, 2.29–2.52)], and small intestine [SIR, 1.62 (95%CI, 1.14–2.23)]. SIR of ureters decreased with age in women. SIR of kidney and renal pelvis decreased before 70 years, and then tends to increased. SIR of lung increased before 60 years, and then tended to decline. SIR of the 3 higher SPCs decreased as prolongation of diagnosis. SIR of small intestine was significantly higher only between 70 and 74 years and within 1 year of diagnosis. Since 2000, SIR of kidney and renal pelvis and lung increased, while that of ureters is relatively stable (Fig. 2A-C, eFigure1A-C, eTable 2).

Standardized incidence ratios of new subsequent primary cancers among bladder cancer survivors by sex (A, B, C), In order to see the fluctuation of the specific second primary cancer more intuitively, we removed the ureteral cancer with the largest fluctuation (this part is mentioned in the supplementary material)

AERM of SPCs varied among BCa survivors. Among men, top 3 SPCs for AERM were prostate (58.41/10000), lung (28.96/10000), and kidney and renal pelvis (9.38/10000). AERM of prostate increased since 2000 and before 70 years old, whereas declined gradually after 70 years old and with prolongation of postdiagnosis period. AERM of lung increased since 2000 and before 75 years old, and then declined. However, it stabilized at different time-points after diagnosis. AERM of kidney and renal pelvis gradually increased in recent years, but has stabilized for different age groups and after 1 year of diagnosis. Among women, top 3 SPCs for AERM were lung (33.43/10000), kidney and renal pelvis (9.90/10000), and ureters (5.37/10000). AERM of lung increased since 2000 and before 70 years old, whereas decreased gradually after 70 years old and with prolongation of diagnosis. AERM of kidney and renal pelvis stabilized after 65 years old and 1 year of diagnosis, and increased since 2000. AERM of ureters increased with age, and is relatively stable after 1 year of diagnosis and since 2000 (Fig. 3A-C, eFigure2A-C).

Absolute excess risk of morbidity of subsequent primary cancers among bladder cancer survivors by sex (A, B, C). In order to see the fluctuation of the specific second primary cancer more intuitively, we removed the prostate cancer with the largest fluctuation (this part is mentioned in the supplementary material)

Incidence of SPCs varied among BCa survivors. Among men, top 3 SPCs for overall incidence were prostate (1131.36/10000), lung (626.53/10000), and colorectal (224.01/10000). Similarly, lung (572.60/10000), breast (388.48/10000), and colorectal (169.66/10000) were the most common in women. Additionally, incidence of SPCs varied with sex between patient’s age group, calendar year, and during follow-up (eFigure. 3). (Fig. 4).

The death of the proportion of subsequent primary cancers among bladder cancer survivors by sex (A, B, C),

The risk of dying from SPCs among BCa survivors is higher in different genders than general population. Among men, the risk of dying from SPCs was 41% higher than the general population, and SMR of 6 of 12 common SPCs were significantly higher. The highest SMR was in ureters [12.12 (95%CI, 10.00–14.56)], kidney and renal pelvis [1.98 (95%CI, 1.82–2.15)], lung [1.54 (95%CI, 1.50–1.59)], and liver [1.29 (95%CI, 1.17–1.43)]. SMR of top 3 SPCs decreased with age, while SMR of liver was significantly higher only in 60–64 and 70–74 age groups. SMR of prostate showed greatest decline, but patients with age > 60 years were not significantly different. SMR of ureters and kidney and renal pelvis decreased with time to diagnosis. SMR of lung after 1 year of diagnosis and liver after 1–10 years of diagnosis were higher than the general population. Since 2005, SMR of ureters gradually increased, SMR of lung gradually decreased, while SMR of kidney and renal pelvis is relatively stable. Among women, the risk of dying from SPCs was 67% higher than the general population, and SMR of 5 of 14 common SPCs were significantly higher. The highest SMR was in ureters [25.82 (95%CI, 18.97–34.33]), kidney and renal pelvis [SMR, 5.07 (95%CI, 4.41–5.80)], cervix [2.49 (95%CI, 1.79–3.36)], and lung [2.03 (95%CI, 1.91–2.15)]. SMR of top 3 SPCs decreased with age. SMR of ureters and kidney and renal pelvis decreased with prolongation of diagnosis, but SMR of ureters was not significantly different in diagnosis of > 10 years. SMR of cervix was significantly higher within 1 year of diagnosis and in 5–10 years. SMR of lung increased after 1 year of diagnosis. Since 2000, SMR of kidney and renal pelvis gradually increased, while SMR of lung was relatively stable (Fig. 5A-C, eFigure. 4 A-C,eTable 3).

Standardized mortality ratios of subsequent primary cancers among bladder cancer survivors by sex (A, B, C). In order to see the fluctuation of the specific second primary cancer more intuitively, we removed the ureteral cancer with the largest fluctuation (this part is mentioned in the supplementary materail

AERD of SPCs varied among BCa survivors. Among men, top 3 SPCs for AERD were lung (15.60/10000), kidney and renal pelvis (2.69/10000), and pancreas (1.28/10000). AERD of lung and kidney and renal pelvis increased from 50 to 80 years old. AERD of pancreas increased after 55 years old. Among women, SPCs with highest AERD were lung (18.66/10000), kidney and renal pelvis (5.44/10000), and ureters (1.45/10000). AERD of lung and kidney and renal pelvis increased from 45 to 70 years old. AERD of ureters increased after 75 years old (eFigure. 5A-C). The mortality of SPCs varied among BCa survivors. Among men, top 3 SPCs for overall mortality were lung (442.58/10000), prostate (117.25/10000), and colorectal (76.99/10000). Similarly, lung (368.56/10000), kidney and renal pelvis (67.80/10000), and colorectal (56.87/10000) were the most common in women (eFigure. 6A-C).