BACKGROUND/RATIONALE:
As an integrated system with access to granular and longitudinal data, the Veterans Health Administration (VHA) is ideally positioned to advance the understanding of the life expectancy, to improve prostate cancer screening strategies, and to generate models of personalized risk-adjusted life expectancy estimates to provide critical information to inform prostate cancer treatment decisions.

Veterans receiving care in the Veterans Health Administration may have higher prostate cancer risk due to a family history, race, or exposure to toxins such as Agent Orange and burn pits. Prostate cancer presents a clinical, health policy, and population health challenge. Prostate cancer is the most common male cancer, presents in older men that may have additional medical conditions, and often follows an indolent course. It is estimated that 60% of all prostate cancer cases represent an "overdiagnosis" of clinically insignificant tumors. For prostate cancer patients, "overdiagnosis" refers to the diagnosis of a disease process that would otherwise not go on to cause symptoms or death. Similarly, "overtreatment" refers to the treatment of prostate cancers that would not otherwise go on to cause symptoms or death.

OBJECTIVE(S):
Our objective is to leverage the power of the standardized electronic health record in the VHA to generate personalized risk-adjusted life expectancy estimates. We will use these estimates to provide critical information to inform prostate cancer screening and treatment medical decision-making. These efforts have the potential to deliver higher quality prostate cancer care, by treating patients most likely to benefit, and while avoiding futile treatment and minimizing treatment-related side effects.

The study include three specific aims.

Aim 1: To develop general and prostate cancer specific life expectancy estimates for maleVeterans receiving care in the VHA.

Aim 2: To develop highly personalized life expectancy estimates as a function of patient-level features including age, race/ethnicity, prior medical claims, disease severity, exposure, health habits, pharmacy, and laboratory data for Veterans with prostate cancer in the VHA.

Aim 3: To evaluate the appropriateness of prostate cancer care in the VHA among men with limited estimated life expectancy.

METHODS:
We will work to develop life expectancy estimates for all male veterans receiving care in the VHA and evaluate how a diagnosis of prostate cancer may modify these estimates. (Aim 1) Next, we use several approaches to generate personalized life expectancy estimates for patients with a diagnosis of prostate cancer. These estimates will use data from the electronic health record including age, race/ethnicity, prior medical claims, disease severity, exposure, health habits, pharmacy, and laboratory data for military beneficiaries receiving care in the VHA. (Aim 2) These estimates will include efforts to use machine learning approaches to generate the best-fitting model of overall survival. Finally, we will estimate the overdiagnosis and overtreatment of prostate cancer in the VHA using the general and personalized life expectancy estimates. (Aim 3)

FINDINGS/RESULTS:
In the first year, we have made steady progress in several areas.

First, we have examined data quality and compared data sources for some important prostate cancer specific variables (e.g., Prostate Specific Antigen). Our group has now shown that there can be errors in the PSA reported by the cancer registry, and that obtaining the PSA directly from the electronic health record is preferable. We have published a study identifying the rate and type of PSA mismatches (Mittikanti et al, JCO, 2016), and recently published a study how cohorts constructed using cancer registry data differ from those using electronic health record data (Guo et al, J Urol, 2018).

Second, we have begun exploring the ethical implications of life expectancy estimation. This work grew directly from comments received during review of the grant. We have now published an editorial exploring the ethical pitfalls of life expectancy estimation in this population (Leppert et al, J Urol, 2018).

Last, we have begun to construct cohorts of prostate cancer patients receiving care in the VHA in order to develop population-wide life expectancy estimates. These simple life tables are nearing completion. Moreover, we are working to develop comorbidity-adjusted life expectancy estimates. We have applied established general measures of comorbidity (e.g., Charlson), as well as the Prostate Cancer Comorbidity Index (manuscript in preparation).

IMPACT:
These efforts have the potential to deliver higher quality prostate cancer care, by treating patients most likely to benefit, and while avoiding futile treatment and minimizing treatment-related side effects.

We also hope to shape the conversation about the ethical considerations when applying life expectancy estimation to prostate cancer screening and treatment.

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External Links for this Project

NIH Reporter

Grant Number: I01HX002126-01A1
Link: https://reporter.nih.gov/project-details/9192674

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PUBLICATIONS:

Journal Articles

1. Sylman JL, Boyce HB, Mitrugno A, Tormoen GW, Thomas IC, Wagner TH, Lee JS, Leppert JT, McCarty OJT, Mallick P. A Temporal Examination of Platelet Counts as a Predictor of Prognosis in Lung, Prostate, and Colon Cancer Patients. Scientific reports. 2018 Apr 26; 8(1):6564. [view]
2. Mittakanti HR, Thomas IC, Shelton JB, Makarov DV, Skolarus TA, Cooperberg MR, Chung BI, Sonn GA, Brooks JD, Leppert JT. Accuracy of Prostate-Specific Antigen Values in Prostate Cancer Registries. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Oct 10; 34(29):3586-3587. [view]
3. Leppert JT. Applying Precision Oncology to Renal Cell Carcinoma: Emerging Challenges. European Urology. 2017 Oct 1; 72(4):565-566. [view]
4. Kirk PS, Borza T, Caram MEV, Shumway DA, Makarov DV, Burns JA, Shelton JB, Leppert JT, Chapman C, Chang M, Hollenbeck BK, Skolarus TA. Characterising potential bone scan overuse amongst men treated with radical prostatectomy. BJU international. 2019 Jul 1; 124(1):55-61. [view]
5. Leppert JT, Mittakanti HR, Thomas IC, Lamberts RW, Sonn GA, Chung BI, Skinner EC, Wagner TH, Chertow GM, Brooks JD. Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind? Urology. 2017 Feb 1; 100:65-71. [view]
6. Lamberts RW, Conti SL, Leppert JT, Elliott CS. Defining the Rate of Negative Ureteroscopy in the General Population Treated for Upper Tract Urinary Stone Disease. Journal of Endourology / Endourological Society. 2017 Mar 1; 31(3):266-271. [view]
7. Leppert JT, Asch SM, Bergman J. Ethical Pitfalls When Estimating Life Expectancy for Patients with Prostate Cancer. The Journal of urology. 2018 Oct 1; 200(4):709-711. [view]
8. Bradshaw C, Thomas IC, Montez-Rath ME, Lorenz KA, Asch SM, Leppert JT, Wang V, O'Hare AM, Kurella Tamura M. Facility-Level Variation in Dialysis Use and Mortality Among Older Veterans With Incident Kidney Failure. JAMA Network Open. 2021 Jan 4; 4(1):e2034084. [view]
9. Bergman J, Schmidt B, Leppert JT. Following Up on an Improperly Drawn Screening Test: The PSA Dilemma. The American journal of medicine. 2021 Mar 1; 134(3):e145-e146. [view]
10. Fan AC, Leppert JT. In Search of Clinical Biomarkers of Response to Checkpoint Inhibitor Therapy in Renal Cell Carcinoma. JAMA Network Open. 2021 Jan 4; 4(1):e2035120. [view]
11. Leppert JT, Lamberts RW, Thomas IC, Chung BI, Sonn GA, Skinner EC, Wagner TH, Chertow GM, Brooks JD. Incident CKD after Radical or Partial Nephrectomy. Journal of the American Society of Nephrology : JASN. 2018 Jan 1; 29(1):207-216. [view]
12. Sohlberg EM, Thomas IC, Yang J, Kapphahn K, Daskivich TJ, Skolarus TA, Shelton JB, Makarov DV, Bergman J, Bang CK, Goldstein MK, Wagner TH, Brooks JD, Desai M, Leppert JT. Life expectancy estimates for patients diagnosed with prostate cancer in the Veterans Health Administration. Urologic oncology. 2020 Sep 1; 38(9):734.e1-734.e10. [view]
13. Lamberts RW, Lines E, Conti SL, Leppert JT, Elliott CS. Minimizing the Cost of Treating Asymptomatic Ureterolithiasis. Urology practice. 2017 Mar 27; 2017(March):https://doi.org/10.1016/j.urpr.2017.03.005. [view]
14. Lamberts RW, Lines E, Conti SL, Leppert JT, Elliott CS. Minimizing the Cost of Treating Asymptomatic Ureterolithiasis. Urology practice. 2018 May 1; 5(3):172-179. [view]
15. Ganesan C, Thomas IC, Romero R, Song S, Conti S, Elliott C, Chertow GM, Tamura MK, Leppert JT, Pao AC. Osteoporosis, Fractures, and Bone Mineral Density Screening in Veterans With Kidney Stone Disease. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2021 May 1; 36(5):872-878. [view]
16. Barbosa PV, Thomas IC, Srinivas S, Buyyounouski MK, Chung BI, Chertow GM, Asch SM, Wagner TH, Brooks JD, Leppert JT. Overall Survival in Patients with Localized Prostate Cancer in the US Veterans Health Administration: Is PIVOT Generalizable? European Urology. 2016 Aug 1; 70(2):227-30. [view]
17. Leppert J, Patel C. Perspective: Beyond the genome. Nature. 2016 Sep 15; 537(7620):S105. [view]
18. Massoudi R, Metzner TJ, Bonneau B, Ngo TC, Shinghal R, Leppert JT. Preclinical Testing of a Combination Stone Basket and Ureteral Balloon to Extract Ureteral Stones. Journal of endourology. 2018 Feb 1; 32(2):96-99. [view]
19. Sonn GA, Fan RE, Ghanouni P, Wang NN, Brooks JD, Loening AM, Daniel BL, To'o KJ, Thong AE, Leppert JT. Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists. European urology focus. 2019 Jul 1; 5(4):592-599. [view]
20. Leppert JT, Brooks JD. Re: Brandon A. Mahal, David D. Yang, Natalie Q. Wang, et al. Clinical and Genomic Characterization of Low-Prostate-specific Antigen, High-grade Prostate Cancer. Eur Urol 2018;74:146-54. European Urology. 2018 Nov 1; 74(5):e110-e111. [view]
21. Dallas KB, Conti S, Liao JC, Sofer M, Pao AC, Leppert JT, Elliott CS. Redefining the Stone Belt: Precipitation Is Associated with Increased Risk of Urinary Stone Disease. Journal of endourology. 2017 Nov 1; 31(11):1203-1210. [view]
22. Vilson FL, Schmidt B, White L, Soerensen SJC, Ganesan C, Pao AC, Enemchukwu E, Chertow GM, Leppert JT. Removing Race from eGFR calculations: Implications for Urologic Care. Urology. 2022 Apr 1; 162:42-48. [view]
23. Cohen JB, Cohen DL, Herman DS, Leppert JT, Byrd JB, Bhalla V. Testing for Primary Aldosteronism and Mineralocorticoid Receptor Antagonist Use Among U.S. Veterans : A Retrospective Cohort Study. Annals of internal medicine. 2021 Mar 1; 174(3):289-297. [view]
24. Kirk PS, Borza T, Shahinian VB, Caram MEV, Makarov DV, Shelton JB, Leppert JT, Blake RM, Davis JA, Hollenbeck BK, Sales A, Skolarus TA. The implications of baseline bone-health assessment at initiation of androgen-deprivation therapy for prostate cancer. BJU international. 2018 Apr 1; 121(4):558-564. [view]

Journal Other

1. Vander VN, Guerin A, Ionescu-Ittu R, Shi S, Wu E, Lin S, Hsu L, Kai-Uwe S, de Ducia S, Wang J, Li S, Derleth C, Liu S, Shi L, Leppert JT. Comparative effectiveness of non-cisplatin (cis)-based first-line (1L) regimens in patients with metastatic urothelial carcinoma (mUC): Veterans Affairs control cohorts vs. IMvigor210. [Abstract]. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018 Feb 6; 36(6):abstract 496. [view]
2. Metzner TJ, Leppert JT. Editorial Comment. [Editorial]. Urology. 2017 Feb 1; 100:156-157. [view]

DRA: Cancer
DRE: Treatment - Observational, Prognosis, TRL - Applied/Translational
Keywords: Cancer, Guideline Development and Implementation, Predictive Modeling, Research Measure Development, Statistical Methods, Surveillance
MeSH Terms: none