Association between Androgen Deprivation Therapy and Risk of Dementia in Men with Prostate Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Data Sources
2.2. Study Population
2.3. Exposures and Outcomes
2.4. Covariates
2.5. Statistical Analysis
2.6. Sub-Analysis and Sensitivity Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Taiwan | UK | |||||
---|---|---|---|---|---|---|
Covariates | ADT | ADT- Naïve | SMD | ADT | ADT- Naïve | SMD |
Number of patients | 8743 | 8743 | 14,949 | 14,949 | ||
Age, y (SD) | 70.3 (8.9) | 69.8 (8.9) | 0.06 | 70.0 (8.5) | 69.2 (8.8) | 0.10 |
Age group, y, n (%) | ||||||
<65 | 2510 (28.7) | 2471 (28.3) | 0.06 | 4525 (30.3) | 4484 (30.0) | 0.02 |
65–74 | 3581 (41.0) | 3643 (41.7) | 6738 (45.1) | 6830 (45.7) | ||
75–84 | 2181 (24.9) | 2180 (24.9) | 2965 (19.8) | 2966 (19.8) | ||
≥85 | 471 (5.4) | 449 (5.1) | 721 (4.8) | 669 (4.5) | ||
Comorbidity, n (%) | ||||||
Hypertension | 4597 (52.6) | 4528 (51.8) | 0.02 | 5956 (39.8) | 6074 (40.6) | −0.02 |
Coronary heart disease | 1659 (19.0) | 1700 (19.4) | −0.01 | 2278 (15.2) | 2252 (15.1) | 0.005 |
Heart failure | 348 (4.0) | 315 (3.6) | 0.02 | 457 (3.1) | 489 (3.3) | −0.01 |
Atrial fibrillation | 199 (2.3) | 208 (2.4) | −0.01 | 846 (5.7) | 878 (5.9) | −0.01 |
Peripheral arterial disease | 247 (2.8) | 255 (2.9) | −0.01 | 439 (2.9) | 454 (3.0) | −0.01 |
Ischemic stroke | 851 (9.7) | 868 (9.9) | −0.01 | 509 (3.4) | 498 (3.3) | 0.004 |
Diabetes mellitus | 1804 (20.6) | 1896 (21.7) | −0.03 | 1502 (10.0) | 1577 (10.5) | −0.02 |
Chronic obstructive pulmonary disease | 1087 (12.4) | 1086 (12.4) | <0.001 | 828 (5.5) | 791 (5.3) | 0.01 |
Chronic kidney disease | 1037 (11.9) | 1054 (12.1) | −0.01 | 1256 (8.4) | 1311 (8.8) | −0.01 |
Chronic liver disease | 1119 (12.8) | 1128 (12.9) | <−0.001 | 252 (1.7) | 284 (1.9) | −0.02 |
Traumatic brain injury | 155 (1.8) | 139 (1.6) | 0.01 | 143 (1.0) | 172 (1.2) | −0.02 |
Depression | 278 (3.2) | 301 (3.4) | −0.01 | 2132 (14.3) | 2236 (15.0) | −0.02 |
Co-medication, n (%) | ||||||
NSAID | 6414 (73.4) | 6418 (73.4) | <−0.001 | 3198 (21.4) | 3296 (22.0) | −0.02 |
Aspirin | 2043 (23.4) | 2078 (23.8) | −0.01 | 3532 (23.6) | 3530 (23.6) | <0.001 |
Clopidogrel | 317 (3.6) | 313 (3.6) | <0.001 | 383 (2.6) | 410 (2.7) | −0.01 |
COX-2 inhibitor | 888 (10.2) | 896 (10.2) | <−0.001 | 229 (1.5) | 237 (1.6) | −0.004 |
Anticoagulant agents | 149 (1.7) | 150 (1.7) | <−0.001 | 662 (4.4) | 688 (4.6) | −0.01 |
Statin | 1705 (19.5) | 1790 (20.5) | −0.02 | 5027 (33.6) | 5136 (34.4) | −0.02 |
Oral hypoglycemic agents | 1463 (16.7) | 1531 (17.5) | −0.02 | 978 (6.5) | 1006 (6.7) | −0.01 |
Insulin | 306 (3.5) | 326 (3.7) | −0.01 | 211 (1.4) | 228 (1.5) | −0.01 |
ACEi/ARB | 3041 (34.8) | 3037 (34.7) | <0.001 | 4438 (29.7) | 4565 (30.5) | −0.02 |
Antidepressants | 1192 (13.6) | 1223 (14.0) | −0.01 | 1528 (10.2) | 1582 (10.6) | −0.01 |
Antipsychotics | 729 (8.3) | 729 (8.3) | <0.001 | 437 (2.9) | 466 (3.1) | −0.01 |
Benzodiazepines | 3420 (39.1) | 3561 (40.7) | −0.03 | 1189 (8.0) | 1212 (8.1) | −0.01 |
Beta-blocker | 2216 (25.3) | 2253 (25.8) | −0.01 | 2530 (16.9) | 2567 (17.2) | −0.01 |
CCB | 3265 (37.3) | 3210 (36.7) | 0.01 | 3318 (22.2) | 3359 (22.5) | −0.01 |
Follow-up years, y, mean (SD) | 4.3 (2.2, 7.3) | 4.2 (2.1, 7.2) | ---- | 5.3 (4.0) | 5.6 (4.1) | ----- |
Taiwan | UK | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Patients | Events | Follow-Up (Person–Years) | Incidence Rate (per 103 Person–Years) | Adjusted HR (95% CIs) | Patients | Events | Follow-Up (Person–Years) | Incidence Rate (per 103 Person–Years) | Adjusted HR (95% CIs) | |
Main analysis | ||||||||||
ADT-naïve group | 8743 | 121 | 44,181.7 | 2.74 | Reference | 14,949 | 237 | 84,331.1 | 2.81 | Reference |
ADT group | 8743 | 134 | 44,291.4 | 3.03 | 1.12 (0.87, 1.43) | 14,949 | 220 | 78,765.1 | 2.79 | 1.02 (0.85, 1.23) |
Subgroup Analysis by Type of ADT | ||||||||||
GnRH agonist-based ADT | ||||||||||
ADT-naïve group | 8461 | 121 | 42,675 | 2.84 | Reference | 14,440 | 236 | 81,058.3 | 2.91 | Reference |
ADT group | 8461 | 75 | 36,614.8 | 2.05 | 0.78 (0.59, 1.05) | 14,440 | 212 | 75,733.0 | 2.80 | 0.99 (0.83,1.20) |
Oral antiandrogens only | ||||||||||
ADT-naïve group | 7087 | 114 | 35,523.9 | 3.21 | Reference | 2921 | 44 | 15,909.1 | 2.77 | Reference |
ADT group | 7087 | 171 | 42,947.8 | 3.98 | 1.18 (0.93, 1.49) | 2921 | 48 | 14,827.8 | 3.24 | 1.15 (0.77, 1.74) |
Subgroup Analysis by Duration of ADT | ||||||||||
<6 months | ||||||||||
ADT-naïve group | 3792 | 68 | 18,420.9 | 3.69 | Reference | 10,577 | 184 | 57,378.2 | 3.21 | Reference |
ADT group | 3792 | 37 | 12,844.8 | 2.88 | 0.88 (0.59, 1.32) | 10,577 | 161 | 44,899.3 | 3.59 | 1.14 (0.93, 1.41) |
6–12 months | ||||||||||
ADT-naïve group | 2987 | 55 | 14,497.9 | 3.79 | Reference | 7661 | 138 | 39,960.7 | 3.45 | Reference |
ADT group | 2987 | 41 | 9135.0 | 4.49 | 1.27 (0.85, 1.91) | 7661 | 117 | 27,875.2 | 4.20 | 1.39 (1.09, 1.79) |
13–18 months | ||||||||||
ADT-naïve group | 1928 | 39 | 10,112.9 | 3.86 | Reference | 4040 | 71 | 21,181.0 | 3.35 | Reference |
ADT group | 1928 | 19 | 5814.1 | 3.27 | 1.08 (0.62, 1.88) | 4040 | 73 | 19,829.6 | 3.68 | 1.25 (0.90, 1.74) |
19–24 months | ||||||||||
ADT-naïve group | 1807 | 33 | 10,056.5 | 3.28 | Reference | 2158 | 39 | 11,252.8 | 3.47 | Reference |
ADT group | 1807 | 23 | 6775.2 | 3.40 | 1.19 (0.70, 2.05) | 2158 | 44 | 12,301.5 | 3.58 | 1.21 (0.78, 1.89) |
>24 months | ||||||||||
ADT-naïve group | 5287 | 87 | 32,687.3 | 2.66 | Reference | 4769 | 87 | 26,349.6 | 3.30 | Reference |
ADT group | 5287 | 42 | 30,348.2 | 1.38 | 0.59 (0.40, 0.85) | 4769 | 108 | 41,467.0 | 2.60 | 0.68 (0.52, 0.91) |
Taiwan | UK | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Patients | Events | Follow-Up (Person-Years) | Incidence Rate (per 103 Person-Years) | Adjusted HR (95% CIs) | Patients | Events | Follow-Up (Person-Years) | Incidence Rate (per 103 Person-Years) | Adjusted HR (95% CIs) | |
Analysis by PS with multivariate adjustment | ||||||||||
ADT-naïve group | 8745 | 121 | 44,190.8 | 2.74 | Reference | 17,040 | 243 | 97,787.1 | 2.48 | Reference |
ADT group | 30,900 | 513 | 149,436.5 | 3.43 | 0.98 (0.80, 1.20) | 30,970 | 525 | 150,495.2 | 3.49 | 1.02 (0.87, 1.19) |
Analysis by PS with IPTW | ||||||||||
ADT-naïve group | 8780.4 | 156.4 | 42,884.6 | 3.65 | Reference | 17,199 | 296 | 92,189.7 | 3.21 | Reference |
ADT group | 30,882 | 494.0 | 150,845.5 | 3.27 | 0.91 (0.76, 1.09) | 30,912 | 484 | 156,175.6 | 3.09 | 0.99 (0.86, 1.14) |
Analysis by PS with SMRW | ||||||||||
ADT-naïve group | 24,442.8 | 414.5 | 121,389.2 | 3.41 | Reference | 29,596 | 575 | 156,092.1 | 3.68 | Reference |
ADT group | 30,900 | 513.0 | 149,436.5 | 3.43 | 1.03 (0.90, 1.17) | 30,970 | 525 | 150,495.2 | 3.49 | 0.98 (0.87, 1.10) |
Cause-specific hazard model | ||||||||||
ADT-naïve group | 8743 | 121 | 44,181.7 | 2.74 | Reference | 14,949 | 237 | 84,331.1 | 2.81 | Reference |
ADT group | 8743 | 134 | 44,291.4 | 3.03 | 1.12 (0.88, 1.43) | 14,949 | 220 | 78,765.1 | 2.79 | 1.02 (0.85, 1.23) |
Sub-distribution hazard model | ||||||||||
ADT-naïve group | 8743 | 121 | 44,181.7 | 2.74 | Reference | 14,949 | 237 | 84,331.1 | 2.81 | Reference |
ADT group | 8743 | 134 | 44,291.4 | 3.03 | 0.93 (0.73, 1.20) | 14,949 | 220 | 78,765.1 | 2.79 | 0.85 (0.71,1.02) |
1-year landmark period | ||||||||||
ADT-naïve group | 11,903 | 199 | 80,477.0 | 2.47 | Reference | 15,738 | 283 | 91,334.5 | 3.099 | Reference |
ADT group | 11,903 | 180 | 67,640.7 | 2.66 | 1.12 (0.95, 1.32) | 15,738 | 275 | 82,845.1 | 3.319 | 1.12 (0.95, 1.32) |
2-year landmark period | ||||||||||
ADT-naïve group | 9382 | 161 | 70,109.1 | 2.30 | Reference | 12,885 | 244 | 72,094.0 | 3.38 | Reference |
ADT group | 9382 | 138 | 61,166.0 | 2.26 | 1.16 (0.93, 1.47) | 12,885 | 218 | 66,517.8 | 3.28 | 1.003 (0.84, 1.20) |
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Liu, J.-M.; Shen, C.-Y.; Lau, W.C.Y.; Shao, S.-C.; Man, K.K.C.; Hsu, R.-J.; Wu, C.-T.; Lai, E.C.-C. Association between Androgen Deprivation Therapy and Risk of Dementia in Men with Prostate Cancer. Cancers 2021, 13, 3861. https://doi.org/10.3390/cancers13153861
Liu J-M, Shen C-Y, Lau WCY, Shao S-C, Man KKC, Hsu R-J, Wu C-T, Lai EC-C. Association between Androgen Deprivation Therapy and Risk of Dementia in Men with Prostate Cancer. Cancers. 2021; 13(15):3861. https://doi.org/10.3390/cancers13153861
Chicago/Turabian StyleLiu, Jui-Ming, Chin-Yao Shen, Wallis C. Y. Lau, Shih-Chieh Shao, Kenneth K. C. Man, Ren-Jun Hsu, Chun-Te Wu, and Edward Chia-Cheng Lai. 2021. "Association between Androgen Deprivation Therapy and Risk of Dementia in Men with Prostate Cancer" Cancers 13, no. 15: 3861. https://doi.org/10.3390/cancers13153861
APA StyleLiu, J. -M., Shen, C. -Y., Lau, W. C. Y., Shao, S. -C., Man, K. K. C., Hsu, R. -J., Wu, C. -T., & Lai, E. C. -C. (2021). Association between Androgen Deprivation Therapy and Risk of Dementia in Men with Prostate Cancer. Cancers, 13(15), 3861. https://doi.org/10.3390/cancers13153861