The Evolving Role of PSA for Prostate Cancer. The Evolving Role of PSA for Prostate Cancer: 10/30/2017

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1 The Evolving Role of PSA for Prostate Cancer Adele Marie Caruso, DNP, CRNP Adult Nurse Practitioner Perelman School of Medicine at the University of Pennsylvania November 4, 2017 The Evolving Role of PSA for Prostate Cancer: What you need to know in your primary care and urology practices Prostate Cancer 1

2 Abstract The advent of the prostatic specific antigen (PSA) test in the 1980 s and its role in early prostate cancer detection has evolved in its general application to the male population. Widespread implementation of PSA lead to a significant increase in disease diagnosis yet questions arose regarding its impact on decreasing prostate cancer related death. Abstract The hallmark clinical data is from two randomized prostate-cancer screening trials from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality in the United States and the European Randomized Study of Screening for Prostate-Cancer to evaluate the effect of screening with PSA testing on death rates from prostate cancer. Abstract These randomized trials placed the effectiveness of PSA screening in doubt, prompting the grade D rating (recommendation against PSA-based screening) from the United States preventative Task Force (USPTF). The recommendation is based on the evidence of both the benefits and harms, that the reduction in prostate cancer mortality is very small, and that PSA screening for prostate cancer does not outweigh the harms. 2

3 Abstract While this has had an impact on PSA use contemporarily, its effects are being reassessed. The validity of at least one of the Phase 3 trials has come under further scrutiny, which may suggest reevaluation of the taskforce guidelines we use in every day practice. There have been several reevaluations of the PLCO and European trials as well as various trends and criticisms. Abstract The rise in the presentation of high risk prostate cancer may be in part reflective of a movement away from screening and possibly a reconsideration for the D-grade. The dichotomy between American Urological Association and other society stances on PSA testing, versus the USPTF, is a current dilemma of great magnitude for advanced practice nurses, primary care physicians, urologists and patients prompting ongoing review and shared decision making. Objectives 1. Understand the historical perspective of PSA testing and operational characteristics of PSA as a screening tool. 2. Develop an in depth knowledge of the major clinical trials, and general application of the evidence based data to the population and general clinical practice 3

4 Objectives 3. Appreciate the significant controversies in the current clinical guidelines, and the direct impact these guidelines have on clinical practice patterns, and the need for shared decision making PSA-Historical Perspective First isolated in the seminal fluid in the 1970 s and found to be specific to the prostate. Not demonstrated to be an optimal cancer screening tool. In the absence of other good markers it was employed. What is PSA? PSA Definition Prostate Specific Antigen (PSA)- A Human Kallikren- III protein produced by the prostate measured in the serum in ng/ml. Enzyme made only in the prostate. Organ specific not cancer specific. Normal PSA in males is ng/dl. 4

5 Prevalence Reasonable performance early on due to the prevalence of high stage disease. As the prevalence population was depleted it was less specific because an elevated PSA can be related to multiple causes. PSA Era. Is the PSA Era over? Adaption of PSA for prostate cancer detection. Depleting the prevalence population [Patients w/ high PSA s] Elevated PSA PSA normally increases with age. Prostatitis/or UTI Benign prostatic hypertrophy Ejaculation Medical procedures i.e. cystoscopy or catheter Prostate Cancer 5

6 PSA Operational Characteristics Value as a screening tool- highly sensitive but not specific. Not an optimal screening test for prostate cancer screening. Implementation in General Practice Widespread implementation of PSA testing lead to an increase in disease diagnosis. Questions arose regarding impact on cancer related death. PSA Banter What s your PSA?? 6

7 PSA- Method of Cancer Detection PSA Actually a method of cancer detection vs. a screening tool. Cost Cost of a PSA test is between $40-80 Cost of prostate needle biopsy $ Cost of treatment of Dx of PCa Radical surgery $12,000-20,000 Radiation $ 50,000-70,000 PCa Statistics Estimates suggest 161,360 new cases of Pca in 2017, representing 19% of all cancers. Estimate predict 26, 730 deaths attributed to Pca representing 8% of all cancers. Siegel et al. CA Cancer J. Clinicians,

8 Role of PSA after surgery Most sensitive method for detecting PSA recurrence after surgery. Undetectable after surgery. If not this represents persistent disease. Rate of rise of PSA suggests the seriousness of the persistence of recurrence. Role of PSA after radiation therapy The nadir PSA may not go to an undetectable level. What constitutes a PSA failure is slightly controversial. Any rise in PSA? The Phoenix criteria- baseline PSA + 2 rises. Abstract & Criticisms No high level evidence to accept or refute the practice of psa testing. 8

9 Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial PLCO was a randomized control cancer screening trial on prostate cancer mortality , 76,696 men were assigned either annual screening for 6 yrs + digital rectal exam (DRE) or usual care- sometimes included screening as control. After 7-10 yrs. of follow up, the rate of death from prostate cancer was low and did not differ significantly b/w the study groups. New England Journal Of Medicine, 2009 PLCO Primary outcome prostate cancer mortality At 7 years, screening was associated with a relative increase of 22% in the rate of prostate cancer diagnosis PLCO NEJM,

10 PLCO NEJM, 2009 European Study Prospective randomized control study of screening for prostate cancer in early 1990 s to evaluate the effect of screening PSA in death rates from prostate cancer. 182,000 men b/w 50 and 74yrs through registries in 7 European countries. Schroder et al. NJEM, 2009 European Study Schroder et al. NEJM,

11 European Study European Study ERSPC PSA-based screening reduced the rate of death from prostate cancer by 20 % but was associated with a high risk of over diagnosis. Schroder et al. NEJM, United States Preventative Task Force (USPSTF) & D Rating What is a Grade D Rating? The USPSTF recommends against the service [against PSA screening]. There is moderate or high certainty that the service has no net benefits or that the harms outweighs the benefits. Implications: discourages the use of this service. Annals of Internal Medicine, 2012; USPSTF,

12 Effect of USPTF & D Rating on PCa screening & Incidence of Dx Retrospective study of the National Cancer Database (NCDB) Jan 2010-Dec % decrease in PCa diagnosis in the first year after the USPSTF grade. Quantifies reduction potential benefits and potential harms. Barocas et al. (2015). Journal of Urology, 194, Effect of USPTF & D Rating on PCa screening & Incidence of Dx Potential benefits Potential harms Reduced harms from over diagnosis and overtreatment of low risk disease and disease found in elderly men Missed opportunities to diagnoses important cancers in men who may benefit from treatment Barocas et al. (2015). Journal of Urology, 194, Effect of USPTF & D Rating on PCa screening & Incidence of Dx The reduction in intermediate & high risk cancer diagnosis raises the concern for delayed diagnosis of important cancers, associated with inferior outcomes, failure to detect higher risk cancers during a window of curability. Barocas et al. (2015). Journal of Urology, 194,

13 Responses of Professional Societies American Academy of Physicians & Canadian Taskforce in 2012 recommended against PSA screening. (AAP- currently reviewing their stance). American College of Physicians in 2013 recommended to discuss screening with men if they had a life expectancy of yrs. Responses of other Professional Societies The American Cancer Society in 2016 recommended SDM and informed discussions about screening at age 50 and earlier for AA men and men with a father or brother with a history of PCa before the age of 65. Clinical Practice Patterns Primary Care Providers- stopped PSA testing! 13

14 Don t Punish the Providers Reevaluation of PLCO Primary outcome- prostate cancer mortality Major criticism- degree of testing in the control group Approximately 90% of men in the control group had undergone at least 1 PSA test. Clarification should be considered wen debating the meaningful use of PSA. Shoag & Mittal. NEJM, 2016 Abstracts and Criticisms When do we treat an individual? The findings change the landscape Self modified management strategies Active surveillance 14

15 AUA Guidelines Early Detection of Prostate Cancer: AUA Guideline, Recommends against PSA screening under the age of 40 (Recommendation; Evidence Grade C). Does not recommend routine screening b/w ages 40 t0 54yrs at average risk (Recommendation; Evidence Grade C). Positive family history or AA race should be individualized. AUA Guideline, 2013 AUA Guidelines For men ages recognizes the decision to undergo PSA screening involves weighing the benefits of preventing PCa mortality in 1 man for every 1000 men screened over a decade against the known potential harms associated with screening and treatment. Strongly recommends SDM for men age that are considering PSA screening, and proceeding based on a man s values and preferences ( Evidence Grade B). AUA Guideline, 2017 AUA Guidelines To reduce the harms of screening, a routine screening interval of two years or more may be preferred for those participating in SDM. Preserves majority of benefits and reduces overdiagnosis and false positives. (Option; Evidence Grade C). The panel does not recommend PSA screening in men age 70+years or any man with less than a year life expectancy. (Recommendation; Evidence Grade C) AUA Guideline,

16 Rise in the presentation of high risk prostate cancer & reconsideration of the USPSTF D Grade New draft recommendations out for Public comment & expired 5/8/2017. Awaiting final recommendations. Draft recommends that providers inform men ages about the potential harms of PSA based screening. USPSTF recommends against PSA screening in men higher that 70 years of age. USPSTF Draft Statement, 2017 Rise in the presentation of high risk prostate cancer & reconsideration of the USPSTF D Grade Special Populations Family History Men wo have 1 st degree relative with advanced CAP at diagnosis, metastatic prostate cancer or who died of PCa (excludes men older that 70 including those with FH USPSTF Draft Statement, 2017 ; National Cancer Institute, 2017 Rise in the presentation of high risk prostate cancer & reconsideration of the USPSTF D Grade African American More likely to develop PCa (203.5 vs cases per 100,000 2 x More likely to die (44.1 vs per 100,000 Earlier onset, more advanced cancer stage at diagnosis, higher rates of more aggressive cancer USPSTF Draft statement, 2017 ; National Cancer Institute,

17 Rise in the presentation of high risk prostate cancer & reconsideration of the USPSTF D Grade USPSTF individualized decision-making so as to understand the potential benefits and harms and to incorporate individual values and preferences Moving closer to AUA recommendations. USPSTF Draft statement, 2017 Prostate Needle Biopsy Shared Decision-Making AUA Document for Shared Decision Making before PSA Screening Quality Measures Status: Public Comment September 26-November 6, 2017 Two Categories Men High Risk Men AUA & AUA s Quality Measure Technical Expert Panel, 2017 [ Not published] 17

18 Reflex Testing Free & Total PSA- Margins 4 K score clinical & labs, reasonable test, do you have high risk cancer Urine Markers clinical & labs tests Pca3 References Andriole, G., Crawford, E. Grubb, R., Buys, S., Chia, D., Church, T., Fouad, M., Berg, C. (2009). Mortality results from a randomized prostate cancer screening trial. New England Journal of Medicine, 360 (13), Barocas, D., Mallin, K., Graves A., Penson, D., Pallis, B., Wincester, D., & Chang, S. (2015). Effect of USPSTF grade D recommendation against screening for prostate cancer on incident prostate cancer diagnosis in the United States. The Journal of Urology, 194, Carter, HB., Albertson, PC., Barry, M. et al. (2013) Early detection of prostate cancer: AUA Guideline. Journal of Urology, 190, 419. Hayes, J. &Barry, M. (2014). Screening for prostate cancer with the prostate specific antigen test: A review of current evidence. Journal of the American Medical Association, 311, (11), References Klotz, L. (2006). Active surveillance with selective delayed intervention favorable risk prostate cancer. Urologic Oncology, 24, Moyer, V. (2012). Screening for prostate cancer: US preventative services task force recommendation statement. Annals of Internal Medicine, 157 (2), National Cancer Institute. (2017). Cancer stat facts; prostate cancer. https;//seer.cancer.gov/statfacts/html/prost.html. Netto, G. (2011). Tumor volume threshold of significant prostate cancer-was Dr. Stamey right all along? The Journal of Urology, 185, Pinsky, P., Blacka, A., Kramer, B., et al. (2010). Assessment contamination and compliance in the prostate component of the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. Clinical Trials, 7,

19 References Shoag, J., Mittal, S., & Hu, J. (2016). Reevaluating PSA testing rates in the PLCO trial. New England Journal of Medicine, 374, Schroder, F., Hugosson, J., Roobol, M., Tammela, T., Ciatto, S., Nelen, V., Kwiatkowski, M. Auvunen, A. (2009). Screening and prostate cancer mortality in a randomized European study. The New England Journal of Medicine,360, Schroder, F., Hugosson, J., Roobol, M., Tammela, T., Zappa, M., Nelen, V., Kwiatkowski, M. Auvienen A. (2014). Screening and prostate cancer mortality: Results of the European randomized studies screening for prostate cancer years of follow-up. The Lancet, 383, References Stamey, T., Caldwell, M., McNeil, J., Nolley, R., Hemenez, M., & Downs. (2004). The prostate specific antigen era in the United States is over for prostate cancer: What happened in the last 20 years? The Journal of Urology, 172, Yuh, L., Dall Era, M., Penson, D., & Evans, C. (2015). Active surveillance f or prostate cancer under the patient protection and affordable care act. Urology Practice, 2 (4), Digital Rectal Examination 19

20 PNBX PNBX Mapping Standard Recommendation Option Clinical Principle Expert Opinion AUA Nomenclature AUA Guideline,