Prostate Biopsy Characteristics: A Comparison Between the Pre- and Post-2012 United States Preventive Services Task Force (USPSTF) Prostate Cancer Screening Guidelines

Original research Prostate Biopsy Characteristics: A Comparison Between the Pre- and Post-2012 United States Preventive Services Task Force (USPSTF) Prostate Cancer Screening Guidelines Navin Shah, MD,1 Vladimir Ioffe, MD,2 Thomas Huebner, MD,3 Ivelina Hristova, BA4 1Mid-Atlantic Urology Associates, Greenbelt, MD; 221st Century Oncology, Greenbelt, MD; 3Integrated Cellular and Molecular Diagnostics, Greenbelt, MD; 4American University, Washington, DC To compare prostate cancer (PCa) characteristics diagnosed by prostate biopsy (Pbx) in the 3 years before and after the 2012 United States Preventive Services Task Force (USPSTF) recommendations for PCa screening, we completed a retrospective comparative analysis of 402 sequential PCa patients diagnosed from 2010 to 2012 (3 years) with 552 PCa patients diagnosed from 2015 to 2017 (3 years). Data was collected on patient age, race, total number of biopsies performed, prostate specific antigen (PSA), Gleason sum score (GSS), and digital rectal examination (DRE). The data was analyzed to determine whether the 2012 USPSTF screening recommendations affected PCa characteristics. Two study groups were defined, Group A and Group B, prior to and after the 2012 USPSTF screening recommendations, respectively. In Group A (pre- 2012 USPSTF recommendations), 567 patients/year underwent a Pbx versus Group B, 398 patients/year, a 30% reduction post-USPSTF. The annual positive Pbx rate for Group A is 134/year versus Group B 184/year, a 37.3% increase post-USPSTF. Group A had high-grade PCa (GSS 7-10) in 51.5% versus Group B in 60.1%, an 8.6% increase post-USPSTF. In Group B, the total number of positive biopsies was increased by 100%. This study shows that in Group B, the Pbx rate decreased by 30% but the annual PCa detection rate increased by 37%. High-grade GSS (7-10) PCa increased by 8.6%. Despite a reduction in the total number of prostate biopsies by 30%, there was a 100% increase in the total number of positive prostate biopsies. [Rev Urol. 2018;20(2):77–83 doi: 10.3909/riu0793] ® © 2018 MedReviews , LLC Vol. 20 No. 2 • 2018 • Reviews in Urology • 77 4170018_05_RIU0793_V2_ptg01.indd 77 9/11/18 5:22 PM Prostate Biopsy Characteristics continued KEY WORDS Prostate cancer • PSA screening • United States Preventive Services Task Force I n 2017, the American Cancer Society reported 161,360 new cases of prostate cancer (PCa) and 26,730 deaths due to PCa in the United States. PCa is the third leading cause of cancer-related deaths among American men. The incidence of PCa among all races is 123.2 (per 100,000 population) it is the highest, 198.4, in African American men, and 114.8 in Caucasian men. The incidence of PCa is the highest in men aged 65 years and older (66%).1 In the 20 years prior to 2012, prostatespecific antigen (PSA)- and digital rectal examination (DRE)-based PCa screening reduced PCa mortality by 50%.2 There are 3 million PCa survivors in the United States.3 In 2008, the United States Preventive Services Task Force (USPSTF) recommended against screening men aged 75 years and older, and, in 2012, the USPSTF recommended against PCa screening for all age groups.4,5 In 2013, the American Urological Association (AUA) recommended against screening men aged 70 years and older.6 Survey data indicate that subsequent to 2013, 50% of primary care doctors did not offer PCa screening to their patients.7 In 2013, national PCa screening decreased by 18%.8 Unfortunately, a 72% rise in metastatic PCa compared with that in 2004 has been reported.9 In 2015, 1400 additional cases of PCa-specific mortality have been documented.10 It is estimated that if the PCa screening is discontinued, 6000 additional deaths due to PCa will occur annually in the United States.11 As the life expectancy for men aged 70 to 80 years is 14.1 to 8.1 years, respectively, an increasing number of men in this age group will be at risk for high-grade PCa.12 A 10-year study of 230,081 American veterans found that 10.5% died from PCa and 77.4% of the PCa deaths occurred in men between the ages of 70 to 89 years.13 In this study, we sought to determine whether PCa diagnoses and cancer characteristics have changed in our community clinical practice after the publication of the 2012 USPSTF recommendations. Methods and Materials In 2014, we published a retrospective analysis of 402 PCa patients diagnosed by prostate biopsy (Pbx).14 The study examined the Pbx characteristics of PCa patients from 2010 to 2012 (3 years). To study the effects of decreased PCa screening, we analyzed an additional 552 PCa cases diagnosed by Pbx from 2015 to 2017 (3 years). Data was collected on patient age, race, number of biopsies, PSA, Gleason sum score (GSS), and DRE. In the current study, we updated Group B to include 3 years of post-USPSTF data. Our original published study contained 18 months of postUSPSTF data.15 All cases are collected from our community clinical practice, a group of 12 board-certified urologists located in Prince George’s County, Maryland, in the Washington, DC metropolitan area. Prostate biopsies were performed on men with a PSA greater than 2.5 ng/mL, an abnormal DRE, or both. Most of the patients had a transrectal ultrasound–guided 12 core Pbx under intravenous sedation on an outpatient basis (a few patients were biopsied under local anesthesia). All patients were cleared for the procedure by their primary care physician. Patient age was stratified as ages under 55, 56 to 69, and 70 to 80 years. The charts of consecutive patients from our practice were reviewed and the information was entered in a database. The data were analyzed to determine whether the 2012 USPSTF screening recommendations affected PCa characteristics. Two study groups were defined: Group A, patients diagnosed prior to the USPSTF screening recommendations (2010-2012), and Group B, patients diagnosed after the USPSTF screening recommendations (2015-2017). We separated the GSS into two groups, GSS 6 and GSS 7 to 10. We defined the GSS 7 to 10 group as aggressive because it harbors a Gleason score 4 or higher component. Chi-squared or Fisher’s Exact Tests were used to compare frequencies. All analyses were conducted using the SAS software program. The study was approved by the Western Institutional Review Board (study number 1087891). Results Prostate Biopsy In the pre-USPSTF period (Group A), 1703 total Pbx were performed over 3 years (Table 1). The PBx rate was 567 biopsies/year. There were 402 positive Pbx over 3 years (23.6%). The annual positive biopsy rate is 134 positive biopsies/ year. In the post-USPSTF period (Group B), there were 1194 total 78 • Vol. 20 No. 2 • 2018 • Reviews in Urology 4170018_05_RIU0793_V2_ptg01.indd 78 9/11/18 5:22 PM Prostate Biopsy Characteristics TABLE 1 Biopsy Statistics in Group A Versus Group B Group A (2010-2012) Group B (2015-2017) Note Total biopsies Annual biopsy rate 1703 567 1194 398 30% reduction Total positive biopsies Annual positive biopsy rate 402 (23.6%) 134/year 552 (46.2%) 184/year 100% relative increase 37% increase Pbx, an annual rate of 398 biopsies/ year. There were 552 positive Pbx (46.2%), an annual rate of 184 positive biopsies/year. In Group B, there was a 100% increase of the total number of positive Pbx (23.6% in Group A vs 46.2% in Group B). Age The age was stratified as under 55, 55-69, and 70 -80 years (Table 2). A comparison was made with group A of 402 PCa patients and group B of 552 PCa patients. In group A, 8.9% were under age 55 years, 56.2% were age 55 to 69 years, and 34.8% were age 70 to 80 years. In group B, 14.5% were under age 55 years, 63% were age 55 to 69 years, and 22% were age 70 to 80 years. The age groups were well matched in both groups. PSA The PSA in group A was under 4 ng/mL in 11.1%, 4 to 9.9 ng/mL in 63.4%, and 10 ng/mL and over in 25.4% (Table 2). In group B, the PSA was under 4 ng/mL in 4.4%, 4 to 9.9 ng/mL in 69.9%, and 10 ng/mL and over in 25.7%. In group B, there were less patients with a PSA under 4 ng/mL compared with group A. Race The study was conducted in Prince George’s County (PGC), Maryland, a county with a three-fold higher prevalence of African Americans (AA) compared with the national average. According to the 2015 American Community Survey, PGC was 61.6% African American, 13.8% white, and 24.6% other races. Our study had an AfricanAmerican representation of 59%, a white representation of 23%, and 18% other races, consistent with the census demographic data (Table 3). Although we were not able to TABLE 2 Comparison of Prostate-specific Antigen (PSA) Levels by Age in Group A Versus Group B Age (years) Group A ,55 56-69 70-80 Total Group B ,55 56-69 70-80 Total n PSA ,4 ng/mL PSA 4-9.9 ng/mL PSA 10 ng/mL and Over 36 226 140 402 5 (13.9%) 23(10.2%) 17 (12.1%) 45 (11.1%) 25 (66.7%) 150 (64.6%) 80 (56.4%) 255 (63.4%) 6 (19.4%) 53 (25.2%) 43 (31.4%) 102 (25.4%) 80 349 125 552 8 (10%) 12 (3.5%) 4 (3.3%) 24 (4.4%) 55 (68.8%) 250 (71.6%) 81 (65.9%) 386 (69.9%) 17 (21.2%) 87 (24.9%) 38 (30.8%) 142 (25.7%) P Value 0.7409 0.0043 0.0261 PSA, prostate-specific antigen. Vol. 20 No. 2 • 2018 • Reviews in Urology • 79 4170018_05_RIU0793_V2_ptg01.indd 79 9/11/18 5:22 PM Prostate Biopsy Characteristics continued TABLE 3 Race by Age in Group B Stratified by Prostate Cancer Positive Versus Negative Biopsy Age PCa positive ,55 56-69 70-80 Total PCa negative ,55 56-69 70-80 Total TOTAL n African American (%) White (%) Other (%) 80 349 123 552 58 (72.5) 236 (67.6) 72 (58.5) 336 (66.3) 13 (16.2) 59 (16.9) 33 (26.8) 105 (19) 9 (11.3) 54 (15.5) 18 (14.6) 81 (14.7) 85 421 136 642 1194 56 (65.9) 213 (50.6) 72 (52.9) 341 (53.1) 707 (59) 14 (16.5) 119 (28.3) 38 (27.9) 171 (26.6) 276 (23) 15 (17.6) 89 (21.1) 26(19.2) 130 (10.3) 211 (17.7) PCa, prostate cancer. extract the race from the data set for Group A because the study data consisted of patients in the same county and in the same urology practice, we assume that the demographics are consistent between Groups A and B. 220 patients in Group B (39.9%) (Table 4). In group A, a GSS of 7 to 10 was found in 207 patients (51.5%) and in 332 patients (60.1%) in Group B. GSS 7 to 10 was higher in Group B by 8.6% when compared with Group A. Gleason Sum Score In Group A, a GSS of 6 was found in 195 patients (48.5%) and in Digital Rectal Examination In Group A, a normal DRE was found in 151 patients and abnormal DRE was found in 251 patients. In Group B, a normal DRE was found in 419 patients and abnormal DRE was found in 133 patients (Table 5) Normal Digital Rectal Examination and Gleason Sum Score In Group A, 78 patients with normal DRE (52%) had GSS of 6 and 73 (48%) had GSS 7 to 10. In TABLE 4 Comparison of Gleason Sum Score (GSS) by Age in Group A Versus Group B Age Group A ,55 56-69 70-80 Total Group B ,55 56-69 70-80 Total n GSS 6 GSS 7-10 36 226 140 402 18 (50.0%) 122 (54%) 55 (39.3%) 195 (48.5%) 18 (50.0%) 104 (46.0%) 85 (60.7%) 207 (51.5%) 80 349 123 552 42 (52.5%) 130 (37.2%) 48 (39.0%) 220 (39.9%) 38 (47.5%) 219 (62.8%) 75 (61.0%) 332 (60.1%) P Value 0.8031 #0.0001* 0.9654 *Statistically significant higher GSS 7-10 in age group 56-69 for Group B vs Group A. 80 • Vol. 20 No. 2 • 2018 • Reviews in Urology 4170018_05_RIU0793_V2_ptg01.indd 80 9/11/18 5:22 PM Prostate Biopsy Characteristics TABLE 5 Comparison of Gleason Sum Score (GSS) by Digital Rectal Exam (DRE) and Age in Group A Versus Group B Age Group A Abnormal DRE ,55 56-69 70-80 Total Normal DRE ,55 56-69 70-80 Total Group B Abnormal DRE ,55 56-69 70-80 Total Normal DRE ,55 56-69 70-80 Total n GSS 6 GSS 7-10 P Value 27 139 85 251 18 (66.7%) 69 (49.4%) 26 (30.9%) 113 (45%) 9 (33.3%) 70 (50.6%) 59 (69.1%) 138 (55%) 9 87 55 151 4 (44.4%) 49 (56.8%) 25 (44.7%) 78 (52%) 5 (55.6%) 38 (43.2%) 30 (55.3%) 73 (48%) 15 75 43 133 8 (53.3%) 21 (28%) 19 (44.2%) 48 (36.1%) 7 (46.7%) 54 (72.0%) 24 (55.8%) 92 (63.9%) 0.3939 0.0022* 0.1280 65 274 80 419 34 (52.3%) 109 (39.8%) 29 (36.3%) 172 (41.1%) 31 (47.7%) 165 (60.2%) 51 (63.7%) 247 (58.9%) 0.7325 0.0067* 0.2834 *Statistically significant difference in GSS 7-10 in Group B vs Group A in the age group 56-69 with a normal or abnormal DRE. Group B, 172 patients with normal DRE (41.1%) had GSS of 6 and 247 (58.9%) had GSS 7 to 10. In patients with a normal DRE, there was a 10.9% increase in GSS 7 to 10 in group B versus group A (58.9% vs 48%, respectively). of 7 to 10 was found in 92 patients (63.9%). Patients with an abnormal DRE had an 8.9% increase in GSS 7 to 10 in Group B versus group A (63.9% vs 55%, respectively). Abnormal Digital Rectal Examination and Gleason Sum Score In Group A, a GSS of 6 was found in 113 patients (45%) and a GSS of 7 to 10 was found in 138 patients (55%). In Group B, a GSS of 6 was found in 48 patients (36.1%) and a GSS The current study reviewed our community-based urologic practice and found that the Pbx rate decreased by 30% in the postUSPSTF period. Additionally, the PCa detection rate was 37% higher post-USPSTF. We also found an 8.6% higher rate of high-grade PCa Discussion (GSS 7-10) in the post-USPSTF period. Despite a 30% reduction in the number of biopsies postUSPSTF guidelines, there was a 100% increase in the total number of positive biopsies. The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) on which the USPSTF based their 2012 recommendation against PCa screening was found to be 90% contaminated and hence should not form the basis of national guidelines.16 Following the 2012 USPSTF recommendations, there was a 64% Vol. 20 No. 2 • 2018 • Reviews in Urology • 81 4170018_05_RIU0793_V2_ptg01.indd 81 9/11/18 5:22 PM Prostate Biopsy Characteristics continued decrease in both DRE screening and a 39% decrease in PSA testing.17 Additionally, other studies have shown that Pbx for cancer have decreased by 21.4% after the 2012 USPSTF recommendations were issued.18 Our study is unique because 59% of the study population were African American (AA), a documented high-risk group. This large percentage of AAs in our study population have certainly factored into our outcomes. This data shows that high-risk populations are disproportionately adversely affected by the 2012 USPSTF guidelines. The 2012 USPSTF guidelines were based on studies in which highrisk populations were underrepresented (only 4% were AA in the PLCO study).19-21 The USPSTF should make available PCa screening for men, especially to high-risk populations including African American men, men with a family history of PCa, and healthy men over age 70 years.22 Since 2013, more locally advanced PCa, metastatic PCa, and PCa-specific deaths have been documented. Weiner and colleagues showed that the incidence of metastatic PCa increased by 72% from 2004 to 2013. The age group from ages 55 to 69 years showed the highest rate of increase (92% increase from 2004-2013).9 The 5-year survival rate in metastatic PCa is 28% and the cost of treating metastatic PCa is well over $100,000.23 More importantly, patients with metastatic PCa have more pain, a much lower quality of life, and almost certain death. The annual cost of the screening PSA test for PCa is $25. We noted that in our pre- and post- 2012 groups, men aged 70 to 80 years had a high GSS of 7 to 10 in 60.7% and 61%, respectively. In our prior study of 5100 US men aged 70 to 80 years with an average PCa risk, patients treated by radiation (external, brachytherapy, or both), 84% of which with a PSA level less than 10 ng/mL, 61% had high a GSS of 7 to 10.24 As surgical series have found that 50% of GSS 6 patients on biopsy are upgraded to GSS 7 to 10 at the time of prostatectomy, it is likely that 80% of our patients aged 70 to 80 years had a GSS of 7 to 10.25,26 Unfortunately, in 2013 the AUA recommended against PCa screening in men aged 70 years and older despite many published studies that documented that these men have more prevalence of PCa, more locally advanced PCa, more metastatic PCa, and more deaths due to PCa.27-29 The current study shows that limiting screening for highrisk men over the age of 70 years is highly counterproductive and harmful. The 2017 USPSTF draft recommendation upgrades PCa screening in men aged 55 to 69 years from a D grade to a C grade, but still excludes men aged 70 years and older. We believe the aforementioned reports strongly indicate that PCa screening should also be made available to detect early PCa in healthy men aged 70 years and over.30 Based on our published data and the peerreviewed literature, we have testified against the 2017 USPSTF’s draft PCa screening guidelines.31 PCa screening is vital for African American men, men with family history of PCa, men aged 70 to 80 years, and for men of lower socioeconomic status, who frequently do not seek medical help until symptoms arise—probably a sign of metastatic disease. Over the past several years, more powerful tools to facilitate PCa detection have entered clinical practice. These include imaging technology such as the multi-parametric prostate MRI and novel genetic and chemical assays that allow clinicians to better focus biopsies at cancerous regions to determine which patients MAin POinTS • The annual prostate biopsy (Pbx) rate decreased by 30% after the 2012 United States Preventive Services Task Force (USPSTF) prostate cancer (PCa) screening guidelines but the annual PCa detection rate increased by 37%. • High-grade Gleason sum score (GSS) (7-10) PCa increased by 8.6% after the 2012 USPSTF recommendations. • Despite a 30% reduction in the total number of biopsies there was a 100% increase in the total number of positive biopsies in the post- 2012 USPSTF guideline period. • These findings suggest that the PCa screening recommendations should be quickly reevaluated to significantly decrease the rising trend of PCa morbidity, mortality, and the cost of prostate cancer treatment. The authors strongly believe that PSA- and DRE-based PCa screening should be made available, especially to AfricanAmerican men, men with a family history of prostate cancer, and healthy men aged 70 years and older. 82 • Vol. 20 No. 2 • 2018 • Reviews in Urology 4170018_05_RIU0793_V2_ptg01.indd 82 9/11/18 5:22 PM Prostate Biopsy Characteristics may harbor cancer despite negative initial biopsy results and which especially to African-American men, men with a family history of prostate PSA- and DRE-based PCa screening should be made available, especially to African-American men, men with a family history of prostate cancer, and healthy men aged 70 years and older. patients are at high risk for aggressive disease.32-34 Moreover, these new diagnostic and risk stratification tools give clinicians guidance to counsel patients regarding active surveillance or treatment. Current prostate cancer research will further clarify which prostate cancers are indolent and thus safe for surveillance and which are aggressive and need to be treated. Diagnosis is the cornerstone of medical care but treatment should be individualized. Not all patients are treated with surgery or radiation as a growing number are actively monitored. The recent findings of increased metastatic prostate cancer is likely the result of decreased prostate cancer screening. Conclusions This study shows that the annual Pbx rate decreased by 30% after the 2012 USPSTF PCa screening guidelines but the annual PCa detection rate increased by 37%. High-grade GSS (7-10) PCa increased by 8.6% after the 2012 USPSTF recommendations. Despite a 30% reduction in the total number of biopsies there was a 100% increase in the total number of positive biopsies in the post- 2012 USPSTF guideline period. These findings suggest that the PCa screening recommendations should be quickly reevaluated to significantly decrease the rising trend of PCa morbidity, mortality, and the cost of prostate cancer treatment. We strongly believe that PSA- and DRE-based PCa screening should be made available, 16. 17. 18. cancer, and healthy men aged 70 years and older. 19. We express our gratitude to Sharon Salenius for her thoughtful review of our manuscript and data analysis. 21. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 20. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67:7-30. Etzioni R, Gulati R. Recent trends in PSA testing and prostate cancer incidence: a look at context. JAMA Oncol. 2016;2:955-956. 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The prostate health index selectively identifies clinically significant prostate cancer. J Urol. 2015;193:1163-1169. Vol. 20 No. 2 • 2018 • Reviews in Urology • 83 4170018_05_RIU0793_V2_ptg01.indd 83 9/11/18 5:22 PM