applied sciences Article Recent Trends in the Diagnostic and Surgical Management of Benign Prostatic Hyperplasia in the U.S. from 2004 to 2017: Annual Changes in the Selection of Treatment Options and Medical Costs Francesco Del Giudice 1,2,† , Jin Kyu Oh 3, *,† , Satvir Basran 2 , Edouard Nicaise 4 , Phil Hyun Song 5 , Wansuk Kim 6 , Sang Youn Kim 7 , Gyeong Eun Min 8 , Koo Han Yoo 8 , Hyuk Jin Cho 9 , Sinyeong Lee 10 , Alessandro Sciarra 1 , Stefano Salciccia 1 , Ettore De Berardinis 1 , Vincenzo Asero 1 , Carlo Maria Scornajenghi 1 , Benjamin Pradere 11 , Wojciech Krajewski 12 , Andrea Gallioli 13 , Matteo Ferro 14 , Felice Crocetto 15 , Savio Domenico Pandolfo 15,16 , Riccardo Autorino 16 , Federico Belladelli 2,17 , Andrea Mari 18 , Gian Maria Busetto 19 , Shufeng Li 2,20 , Simone Crivellaro 21 and Benjamin Inbeh Chung 2 1 Department of Maternal Infant and Urologic Sciences, Sapienza University of Rome, Policlinico Umberto I Hospital, 00161 Rome, Italy 2 Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA 3 Department of Urology, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Korea 4 Department of Urology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Department of Urology, College of Medicine, Yeungnam University, Daegu 42415, Korea 6 Department of Urology, College of Medicine, Inje University, Busan Paik Hospital, Busan 47392, Korea 7 Department of Radiology, Seoul National University Hospital, Seoul 03080, Korea Citation: Del Giudice, F.; Oh, J.K.; 8 Department of Urology, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Basran, S.; Nicaise, E.; Song, P.H.; Gangdong, Seoul 02447, Korea Kim, W.; Kim, S.Y.; Min, G.E.; Yoo, 9 Department of Urology, College of Medicine, Catholic University, Seoul 06591, Korea K.H.; Cho, H.J.; et al. Recent Trends 10 Department of Urology, Seoul Medical Center, Seoul 03080, Korea in the Diagnostic and Surgical 11 Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria Management of Benign Prostatic 12 Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Hyperplasia in the U.S. from 2004 to Wrocław Medical University, 50-367 Wrocław, Poland 2017: Annual Changes in the 13 Department of Urology, Fundació Puigvert, 08025 Barcelona, Spain 14 Department of Urology, European Institute of Oncology, IRCCS, 20141 Milan, Italy Selection of Treatment Options and 15 Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Medical Costs. Appl. Sci. 2022, 12, 8697. https://doi.org/10.3390/ “Federico II”, 80125 Naples, Italy 16 Division of Urology, VCU Health, Richmond, VA 23219, USA app12178697 17 Division of Experimental Oncology, Unit of Urology, Urologicl Research Institute (URI), IRCCS, Academic Editor: Francesca Silvagno Ospedale San Raffaele, 20132 Milan, Italy 18 Oncologic Minimally Invasive Urology and Andrology Unit, Department of Experimental and Clinical Received: 15 July 2022 Medicine, University of Florence, Careggi Hospital, 50134 Florence, Italy Accepted: 26 August 2022 19 Department of Urology and Organ Transplantation, University of Foggia, 71122 Foggia, Italy Published: 30 August 2022 20 Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA 21 Department of Urology, College of Medicine, University of Illinois, Chicago, IL 60612, USA Publisher’s Note: MDPI stays neutral * Correspondence: shaq21@empas.com; Tel.: +82-32-460-3334; Fax: +82-32-460-8340 with regard to jurisdictional claims in † These authors contributed equally to this work. published maps and institutional affil- iations. Abstract: Background: Transurethral resection of the prostate (TURP) is the gold-standard treatment for benign prostatic hyperplasia (BPH). However, laser surgery techniques (e.g., photoselective vaporization of the prostate (PVP), holmium laser, thulium laser enucleation of the prostate (HoLEP Copyright: © 2022 by the authors. or ThuLEP)), and minimally invasive treatment options (e.g., UroLift) are increasingly replacing TURP. Licensee MDPI, Basel, Switzerland. This study seeks to report the annual incidence, management trends, and costs of BPH procedures This article is an open access article in the U.S. Methods: Data analyses of U.S. health insurance claims from 2004 to 2017, collected distributed under the terms and from the de-identified Optum Clinformatics Claims Database, were performed to determine the conditions of the Creative Commons number of BPH patients and the treatment selected. Results: A total of 51,448 patients underwent Attribution (CC BY) license (https:// BPH procedures from 2004 to 2017. There was a significant increase in the annual rate from 770 in creativecommons.org/licenses/by/ 2004 to 6571 in 2017. The mean patient age (±SD) increased from 67.6 years old (±8.4) in 2004 to 4.0/). Appl. Sci. 2022, 12, 8697. https://doi.org/10.3390/app12178697 https://www.mdpi.com/journal/applsci Appl. Sci. 2022, 12, 8697 2 of 12 73.4 years old (±8.4) in 2017. More than 60% of patients underwent cystourethroscopy and a post- void residual urine check for workup prior to surgical management. TURP was the most-common, and PVP was the second-most-common BPH procedure. Medical and total treatment costs increased, while the detection rate of prostate cancer after BPH surgery gradually decreased from 19.87% in 2004 to 5.78% in 2017. Conclusions: Our study demonstrates a recent trend in BPH management that replaces the traditional TURP technique with alternative methods. Due to rising costs, future studies should assess whether these newer methods are cost effective over the long term. Keywords: benign prostatic hyperplasia; surgery; trends 1. Introduction Benign prostatic hyperplasia (BPH) is a common condition afflicting male patients, who may suffer from related lower urinary tract symptoms (LUTS), such as frequency, nocturia, and urgency. Several mechanisms have been reported to affect and aggravate LUTS in BPH patients, including age-related impairment of blood flow in pelvic organs and aggravation in bladder dysfunction [1]. If LUTS are medically uncorrectable, surgical treatment should be considered for otherwise healthy male patients, who suffer from moderate-to-severe outlet-obstructive symptoms. Transurethral resection of the prostate (TURP) is the gold standard for surgical treat- ment of BPH [2]. However, technological advancements in medical device development have provided many alternative surgical options, including photoselective vaporization of the prostate (PVP), holmium laser enucleation of the prostate (HoLEP), thulium laser enucleation of the prostate (ThuLEP), and UroLift. Furthermore, some studies have shown that there are favorable outcomes for using these new BPH surgical techniques instead of TURP [3–6]. In more detail, HoLEP and ThuLEP have demonstrated similar disobstruction out- comes with a comparable International Prostate Symptom Score (IPSS) improvement at both mid- and long-term follow-up, while similarly improving the overall quality of life (QoL) outcomes [7]. Despite these surgical options, which are still considered as possible alternatives (if the equipment and surgical expertise are available) according to interna- tional guidelines, the information regarding the safety profile resulting from the short- and long-term follow-up is in favor of laser-assisted enucleating or vaporesection techniques, making these a possible game changer in case of fragile patients or for those receiving anticoagulant or antiplatelet therapy [8]. Moreover, Salciccia et al. [9] have recently demon- strated how these new available endoscopic surgical techniques, including PVP, can be valid for an outpatient setting, thus, expanding the potentiality of application and the wide distribution of the techniques when compared to TURP. However, these newer modalities, in many cases, may be far more expensive than traditional TURP, and there are few contemporary studies that analyze and compare these costs [10]. Moreover, we have few data regarding the total overall costs incurred from the BPH workup utilized to confirm the need for surgical treatment. Therefore, the aim of our study is to present the annual rates of BPH surgery and to analyze recent trends in the utilization of newer surgical modalities and any changes in medical costs related to these treatments over a 15-year period in the U.S. 2. Materials and Methods The current study was performed with approval from the Center for Population Health Science at Stanford University in the U.S. Patient data collected from the Optum Clinformatics Data Mart Claims Database were derived from commercial and Medicare Advantage health insurance claims. Optum Clinformatics Data Mart is a database com- prised of administrative health claims submitted for payment by providers and pharmacies. These claims are verified, adjudicated, adjusted, and de-identified. Data are included for Appl. Sci. 2022, 12, 8697 3 of 12 only those covered lives, roughly 70 million over a 14-year period, with both medical and prescription drug coverage. Costs are standardized to create standard prices across all provider services. International Classification of Disease Ninth and Tenth Revisions, Clinical Modification (ICD-9-CM, ICD-10-CM) codes, and Current Procedural Terminology (CPT) codes were used to identify the study cohort, treatments, and comorbidities. A comprehensive list of ICD-9/10 and CPT codes summarizing the analytical steps for the data analysis and inclusion/exclusion criteria are presented in Supplementary File S1. This method has been used in other studies [11–14], and, given de-identified information, this study was deemed exempt from informed consent requirements by the Stanford University Medical Center Institutional Review Board. Patients who had undergone BPH surgery (index date) between 2004 and 2017 in the U.S. were reviewed. As per primary aim, only those patients with an associated code for specific BPH surgical procedure were included (i.e., TURP, HoLEP, ThuLEP, UroLift). Trends and distribution over the years of enrolment were analyzed and reported for each single procedure over the time of database enrolment across the U.S. Moreover, as per inclusion criteria, subjects at least 50 years old, with at least 6 months enrolment time before, and 1 month after the index date were further assessed leading to the final of n = 82,458 men. Additionally, patients were considered eligible per final enrolment, only if they had a least one urodynamic, cystourethroscopy, USG, biopsy, uroflowmetry, or surgical urological procedure treatment code. Overall, this led to the final cohort composition of n = 51,448 men. Per the secondary aim of the study, we reviewed the trends in adoption of various diagnostic methods for BPH including urodynamic studies, cystourethroscopy, transrectal ultrasound, prostatic biopsy, uroflowmetry, and the measurement of post-void residual urine volume (PVR). The collected data included patient age, race, household income, educational status, and co-morbidities. In addition, the annual costs of BPH diagnostic and treatment modalities were reviewed from the database for both diagnostic and therapeutic BPH-related procedures. All costs were standardized based on Medicare Relative Value Units and other pricing methods, adjusting for inflation. Finally, incidental diagnoses of prostate cancer (PCa) detected during BPH procedures were recorded over the years to depict the trends in cancer detection and the median prostate specific antigen (PSA) values associated with BPH patients ultimately addressed to surgical disobstruction. Statistical Analysis Patient demographics and the socio-economic and clinical characteristics for those who received diagnostic and/or therapeutic BPH-related procedures were summarized by mean values (standard deviation (SD)), or median values (inter-quartile range (IQR)). Temporal trends with descriptive statistics on the adoption of each explored diagnostic procedure for BPH were presented to assess the number of cases by year and the relative percentages of each adopted procedure. Additionally, temporal trends in median cost per diagnosis and/or treatment were presented and plotted to show the yearly trajectory of the different procedures reviewed. Incidental PCa findings and associated PSA values were recorded and compared by temporal trends. 3. Results The overall number of subjects reviewed included 51,448 patients. Table 1 shows the patients’ characteristics of age, race, household incomes, and educational status by BPH surgery year. Appl. Sci. 2022, 12, 8697 4 of 12 Table 1. Annual characteristics of patients undergoing benign prostatic hyperplasia surgery. 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 Number (n) 770 1306 1762 2212 2942 3741 3920 4057 4305 4818 4344 4873 5827 6571 Age (years), mean (std) 67.6 (8.4) 68.4 (8.2) 69.3 (8.4) 69.7 (8.5) 70.4 (8.8) 71 (8.7) 71.3 (8.7) 71.7 (8.6) 71.9 (8.7) 72 (8.6) 72.6 (8.5) 72.7 (8.6) 72.9 (8.6) 73.4 (8.4) Race, n (%) Asian 18 (2.34) 25 (1.91) 27 (1.53) 34 (1.54) 63 (2.14) 79 (2.11) 80 (2.04) 101 (2.49) 115 (2.67) 139 (2.89) 132 (3.04) 146 (3) 170 (2.92) 190 (2.89) Black, non-Hispanic 76 (9.87) 97 (7.43) 162 (9.19) 149 (6.74) 242 (8.23) 305 (8.15) 353 (9.01) 332 (8.18) 344 (7.99) 357 (7.41) 279 (6.42) 342 (7.02) 487 (8.36) 579 (8.81) 391 432 471 500 637 704 Hispanic 46 (5.97) 86 (6.68) 124 (7.04) 144 (6.51) 254 (8.63) 365 (9.31) 373 (9.19) 470 (9.76) (10.45) (10.03) (10.84) (10.26) (10.93) (10.71) 630 1098 1449 1885 2383 2966 3122 3251 3414 3852 3462 3885 4533 5098 White (81.82) (84.07) (82.24) (85.22) (81.00) (79.28) (79.64) (80.13) (79.3) (79.95) (79.7) (79.73) (77.79) (77.58) Household Incomes, n (%) 212 342 483 616 795 1054 1083 1023 1054 1096 963 995 1235 1298