Transrectal Ultrasound–guided Versus Transperineal Mapping Prostate Biopsy: Complication Comparison

Transrectal ultrasound guided prostate biopsy • Transperieneal mapping prostate biopsy • Complications

Original research Transrectal Ultrasound–guided Versus Transperineal Mapping Prostate Biopsy: Complication Comparison Vassilios M. Skouteris, MD,1 E. David Crawford, MD,2 Vladimir Mouraviev, MD,3 Paul Arangua, MPH,2 Marios Panagiotis Metsinis, MD,1 Michael Skouteris, MD,1 George Zacharopoulos, MD,1 Nelson N. Stone, MD4 1Hygeia Hospital, Prostate Brachytherapy Center, Athens, Greece; 2Department of Surgery/Urology, University of Colorado, Aurora, CO; 3 Department of Urology, The Central Florida Cancer Institute, Davenport, FL; 4Department of Urology, The Icahn School of Medicine at Mount Sinai, New York, NY Herein, the authors compare morbidity in men who underwent both transrectal ultrasound–guided (TRUS) prostate biopsy and transperineal mapping biopsy (TPMB) at two institutions with extensive experience in both procedures. We also identified strategies and predictive factors to reduce morbidity for both procedures. In our study, 379 men from two institutions, of which 265 (69.9%) had a prior TRUS-guided biopsy, also had TPMB performed via a template with biopsies taken at 5-mm intervals. Men in the TRUS group had a median of 12 cores sampled whereas the TPMB group had 51.5 (range, 16-151). The median biopsy density was 1.1 core/cc prostate volume. Median age and prostate-specific antigen (PSA) level were 65 years (range, 34-86) and 5.5 ng/mL (range, 0.02-118). Of these men, 11 of 265 (4.2%) who had TRUS biopsy developed urinary tract infection compared with 3 of 379 (0.79%) of those with mapping biopsy. Infection was 14.8% in TRUS biopsy group with 13 or more cores versus 2.9% in those with 12 or less (OR, 5.8; 95% CI, 1.6-21.2; P 5 0.003). No men developed retention after TRUS biopsy whereas 30 of 379 (7.9%) did following TPMB. Older age, larger prostate volume (PV), and higher core number were associated with retention. On linear regression only age (P 5 0.010) and PV (P 5 0.016) remained as significant associations. Men older than 65 years had 12.8% versus 3.9% (OR, 3.7; 95% CI, 1.6-8.4, P 5 0.001) and PV greater than 42 cc had 13.4% versus 2.7% (OR, 5.7; 95% CI, 2.1-15.1) retention incidence. In the present study TPMB is rarely associated with infection (0.78%) but more commonly with urinary retention (7.9%). Men older than 65 years and with PV greater than 42 cc were at four to five times greater retention risk. Consideration should be given to discharging these men with a urinary catheter following TPMB. [Rev Urol. 2018;20(1):19–25 doi: 10.3909/riu0785] ® © 2018 MedReviews, LLC 4170018_04_RIU0785_V1_rev03.indd 19 Vol. 20 No. 1 • 2018 • Reviews in Urology • 19 5/2/18 12:28 PM Complications of TRUS vs TPMB continued KEY WORDS Transrectal ultrasound guided prostate biopsy • Transperieneal mapping prostate biopsy • Complications T here are more than 3.4 million prostate biopsies performed worldwide per year; of these, more than 95% are performed using transrectal ultrasound (TRUS) guidance.1 Due to its relatively low cancer detection rate of between 35% and 48%, many of the 161,360 men newly diagnosed in the United States in 2017 may in fact be underdiagnosed and thus treated incorrectly due to inaccurate risk stratification.2 The standard systematic 12-core TRUS-guided biopsy remains the most common procedure for newly diagnosed prostate cancer (PCa) with only a minority (less than 5%) performed by the transperineal mapping biopsy (TPMB) route.3 After TRUS biopsy was first introduced and popularized by Hodge and Stamey as a 6-core technique, the number of specimens increased to 12 with lateral-directed biopsies improving the diagnostic yield.4-6 Various investigators have sought to improve its accuracy by sampling 20 or more sites, but most urologists have maintained the 12-core biopsy TRUS approach as the standard of care.3,7 Despite these changes, serious problems remain with the TRUS approach. Thirty percent of biopsies need repeating because of falsenegative results and as many as 50% of cases may be mischaracterized.8 A TRUS biopsy Gleason score of 6 is upgraded in 30% to 40% of men undergoing radical prostatectomy (RP), contributing to unnecessary overtreatment such as RP or radiation in 40% of patients.9-11 Of those electing active surveillance, 45% were switched to definitive therapy within 5 years because of tumor progression or patient concern (eg, PSA anxiety) that may suggest an incorrect staging in some cases after primary standard systematic biopsy.12 Finally, an increasing incidence of post-procedure infection and sepsis is of great concern for clinicians and patients.13 To improve the diagnostic accuracy of prostate biopsy, some urologists have switched to the TPMB procedure, either as the confirmatory biopsy after a diagnosis of lowrisk disease, as an improved staging procedure, or, in some cases, as the primary biopsy.14 The TPMB has been shown to more closely represent disease found at RP and has improved risk stratification.15 Although the advantages of TPMB have been well documented, it is associated with a different risk profile than TRUS biopsy.16 It has been shown, mostly in the retrospective studies from the body of the literature, that while there was a significant reduction of severe febrile urinary tract infection (UTI) with bacteremia/urosepsis, the rate of acute urinary retention was increased due to more extensive sampling of prostate with multiple cores taken. Herein, we compare the morbidity in men who underwent both TRUS and TPMB at two institutions with extensive experience in both procedures. We also identified strategies and predictive factors to reduce morbidity for both procedures. Methods The dataset included 379 men from two institutions—206 from the University of Colorado Anschutz Medical Campus (UCAMC; Aurora, CO), and 173 from Hygeia Hospital (HH), Athens, Greece. Of these, 265 men (69.9%) had previous primary (screening) TRUSguided biopsy prior to TPMB and 114 had TPMB as the initial biopsy at the discretion of urologist. Of the 206 men from UCAMC, 200 (97.1%) had a prior TRUS biopsy compared with 108 (62.4%) from HH. Men with either one or multiple prior negative TRUS biopsies (n 5 176) were referred for TPMB for a more definitive biopsy. There was a median of 1.0 prior TRUS biopsy procedure performed (range, 1-7) prior to having the TPMB, which included 15.2% with more than two biopsies. All TRUS procedures were performed with either an 18 or 16G coaxial biopsy device with a 17- to 20-mm core bed. Patients with a positive TRUS biopsy (n 5 89) underwent TPMB for intra-prostatic staging prior to focal therapy consideration. The TPMB was performed under anesthesia by a single surgeon at each institution through a brachytherapy template with biopsies taken at 5-mm intervals.17 Multiple in-line samples (up to 3) were taken if prostate length exceeded 2 cm. Men with prior TRUS had a median of 12 cores sampled (range, 6-46). A median of 51.5 (range, 16-151) cores were retrieved in the TPMB group. The pathologic evaluation of prostatic cores was performed by experienced uropathologists at both institutions with no centralized review. The median prostate volume was 42 cc (range, 9-178) and the median biopsy density was 1.1 core/cc prostate volume. The TRUS and the TPMB patients were given fluoroquinolone prophylaxis (ciprofloxacin) 20 • Vol. 20 No. 1 • 2018 • Reviews in Urology 4170018_04_RIU0785_V1_rev03.indd 20 5/2/18 12:28 PM Complications of TRUS vs TPMB prior to and for a short time after the procedures. A urinary catheter was placed at the time of the mapping biopsy that was removed either in the recovery room (HH) or the next day (to a maximum of 48 hours at UCAMC). If the patient failed a voiding trial in the recovery room or after removal in the clinic and was sent home with a catheter, the patient was considered to have urinary retention. Patients presenting with post-biopsy urinary symptoms or fever and who had a positive culture were classified as infected. The study was approved by the internal review board at UCAMC for data collection and reporting. Statistical Analysis Associations between urinary infection and retention were compared for TRUS and TPMB with age, core number, PV, and prior TRUS-guided biopsy number (number of cores and procedures) by ANOVA and chi-square. Multiple significant associations were compared by linear regression. Statistical analysis was performed using SPSS v.20. Results Median age and PSA were 65 years (range, 34-86) and 5.5 ng/mL (6.83; range, 0.1-118; Table 1). Eighty-nine of 265 men (33.6%) were diagnosed with prostate cancer by TRUS versus 240 of 379 men(63.3%) by TPMB. Eleven of 265 (4.2%) of the men who had TRUS biopsy developed UTIs compared with 3 of 379 (0.79%) of those with mapping biopsy. Age (P 5 0.251), the number of TRUS biopsy procedures (P 5 0.692), or PV (P 5 0.081) were not associated with infections. Men with infection had a mean of 19.3 TRUS cores versus 12.7 in those without infection (P , 0.001). Infection was 14.8% in men with 13 or more cores versus 2.9% in those with 12 cores or less (OR, 5.8; 95% CI, 1.6-21.2; P 5 0.003). In contrast, none of these factors were associated with infection following TPMB. Two of the 3 men who developed infection after mapping also had post-TPMB urinary retention. Infection occurred in 1 of 349 (0.3%) of those without retention versus 2 of 30 (6.7%) in those who developed retention (OR, 24.9; 95% CI, 2.2-28.2; P , 0.001). No men developed retention after TRUS biopsy, whereas 30 of 379 (7.9%) did following TPMB. Retention was 5.8% at UCAMC and 10.4% at HH (P 5 0.100; Table 2). Older age, larger PV, and higher core number were associated with urinary retention. To determine if the UCAMC policy of keeping a urinary catheter routinely for 1 to 2 days following the mapping procedure versus removing the catheter in the recovery room, A separate analysis of risk factors for retention was completed. Linear regression revealed age (P 5 0.010) and PV (P 5 0.016) as significant predictive factors, whereas the number of cores removed and the institution where biopsy was performed were not significant (Table 3). Retention was 12.8% in men older than 65 years versus 3.9% for the younger men (OR, 3.7; 95% CI, 1.6-8.4; P 5 0.001). Those with prostate volume greater than 42 cc (median size) had 13.4% versus 2.7% retention incidence for men with smaller prostates (OR, 5.7; 95% CI, 2.1-15.1). There was no difference in retention incidence for men with PV # 42 cc (P 5 0.582) or larger (P 5 0.731) between the TABLE 1 Patient Characteristics in Men Undergoing TRUS and TPMB UCAMC HH Total P Value Age (years) PSA (ng/mL) PSAD No. cores TRUS 63 (34-78) 5.9 (0.1-41.8) 0.162 (0.1-1.072) 11.9 (6-18) 66.2 (40-86) 7.9 (2-118) 0.165 (0.1-3.576) 15.8 (6-46) 64.4 (36-86) 6.8 (0.1-118) 0.163 (0.1-3.576) 12.8 (6-46) 0.071 0.414 0.902 ,0.001 Prostate volume (cc) 39.5 (9-110) 56.6 (20-178) 47.4 (9-178) ,0.001 No. cores TPMB No. positive cores TPMB 68.1 (16-151) 6.4 (1-31) 45.3 (17-84) 7.4 (1-37) 57.6 (16-151) 6.7 (1-37) ,0.001 0.227 Variable Values are mean and range. There were 206 TPMB performed at UCAMC and 173 at Hygeia Hospital. HH, Hygeia Hospital; PSA, prostate-specific antigen; PSAD, prostate-specific antigen density; TPMB, transperineal mapping biopsy; TRUS, transrectal ultrasound– guided prostate biopsy; UCAMC, University Colorado Anschutz Medical Campus. Vol. 20 No. 1 • 2018 • Reviews in Urology • 21 4170018_04_RIU0785_V1_rev03.indd 21 5/2/18 12:28 PM Complications of TRUS vs TPMB continued TABLE 2 Association With Age, Prostate Size, and Number of TPMB Cores in Men With Urinary Retention Variable Age (years) UCAMC Retention No retention P value HH Retention No retention P value Total Retention No retention P value Prostate Size (cc) No. Cores 69.3 62.6 0.003 48.2 38.9 0.054 68 66.9 0.009 69.4 65.8 0.079 72.2 54.5 ,0.001 53.8 44.4 0.003 69.4 64.0 ,0.001 64.4 45.9 ,0.001 67.2 56.7 0.023 HH, Hygeia Hospital; TPMB, transperineal mapping biopsy; UCAMC, University Colorado Anschutz Medical Campus. TABLE 3 Linear Regression With Urinary Retention as Dependent Variable 95.0% Confidence Interval HR Model (urinary retention) HR Sig Lower Bound Upper Bound Age (years) 0.134 0.010 .001 .008 Prostate size (grams) 0.157 0.016 .000 .004 Total number of cores Site: UCAMC vs HH 0.100 0.041 0.135 0.558 .000 2.053 .003 .098 HH, Hygeia Hospital; HR, hazard ratio; UCAMC, University Colorado Anschutz Medical Campus. two institutions. Two men (0.5%) required hospitalization for gross hematuria. Discussion TRUS-guided prostate biopsy remains the most common type of urological procedure performed in the office.1 Although it is considered a safe procedure, minor complications such a hematuria, hematospermia, rectal bleeding, and voiding symptoms occur in about half of patients.3 Major complications include serious infections (febrile UTI with bacteremia or urosepsis), urinary retention, and significant bleeding.13 The infection rate is on the rise, reflecting an increasing prevalence of “superbugs” such as fluoroquinolone-, carbapenem-, or multidrug-resistant enterobacteriaceae such as Escherichia coli and Bacteroides.18 Nam and colleagues conducted a population-based study of 75,190 men who underwent a TRUS-guided biopsy in Ontario, Canada, between 1996 and 2005.19 The 30-day hospital admission rate increased from 1.0% in 1996 to 4.1% in 2005 (P , 0.0001). Most hospital admissions (72%) were for infection-related reasons. The probability of being admitted to the hospital within 30 days of having the procedure increased fourfold between 1996 and 2005. 22 • Vol. 20 No. 1 • 2018 • Reviews in Urology 4170018_04_RIU0785_V1_rev03.indd 22 5/2/18 12:28 PM Complications of TRUS vs TPMB The results of a large prospective study under the umbrella of European Randomized Study of Screening for Prostate Cancer (ERSPC) included 10,474 men undergoing TRUS-guided prostate biopsy from 1993 to 2011 demonstrated a febrile infection rate of 4.2% and a hospital readmission rate of 0.8%, 81% of these for infection.20 According to a metaanalysis of the literature based on 7000 records, the occurrence of serious complications after TRUSguided biopsy requiring hospital The TPMB approach was introduced to better characterize the type, amount, and spatial distribution of cancer inside the prostate, especially for quickly implemented focal ablative therapy. Many studies have documented both an increase in cancer detection rate and precise spatial cancer distribution after TPMB as a primary biopsy or as a confirmatory biopsy in men on active surveillance.29-31 Furthermore, it has been also utilized to determine presence of cancer in men at higher risk (eg, with While many studies in the literature have not demonstrated an increased risk of UTI after different saturation techniques, our data suggested that men with more than 12 cores taken via TRUS biopsy may be at an additional increased risk for infection. admission primarily due the infection ranged from 0.5% to 6.9% depending upon the antimicrobial prophylactic regimen.21 This rate has slowly increased over the time. While many studies in the literature have not demonstrated an increased risk of UTI after different saturation techniques, our data suggested that men with more than 12 cores taken via TRUS biopsy may be at an additional increased risk for infection.22-26 For instance, the infection rate was 6 times higher in a cohort of patients with 13 or more cores than in those who had standard 12 cores (median core number). Simsir and colleagues also demonstrated an increased risk of infection with a greater number of sampled biopsy cores.27 Other studies, however, failed to demonstrate an increased risk of UTI after different saturation techniques.23-27 It may be prudent in the current era of fusion biopsy, where physicians perform 2 to 4 target cores as well as 12 systematic biopsies, for urologists to be aware of the possible increased infection risk and consider additional prophylactic measures.28 rising PSA or other new genomic biomarkers) after negative TRUSguided or fusion MRI-TRUS– guided biopsy.13,21 The incidence of clinically significant UTI, especially including fever with positive blood culture (urosepsis) requiring currently reported for TRUSguided biopsy. 20,26,33 The most serious complication reported after TPMB is acute urinary retention (AUR), affecting up to 12.5% of the cases.22,23,26,32,34,35 This is significantly greater than the risk of AUR with TRUS-guided biopsies, which in a systematic review was reported as a range from 0% to 3.1% (Table 4).19,20,33,36-38 This higher risk of urinary retention when compared with conventional TRUS-guided biopsies can be explained by the greater amount of core biopsies taken during TPMB, which results in intra-prostatic swelling from bleeding. This is similar to what is often seen following prostate brachytherapy, where an average of 30 needles are inserted to deliver the radioactive source.39 AUR following TPMB is mainly managed conservatively, with the majority of patients responding to a trial without a catheter within a few days post-procedure. Muthuveloe and colleagues also found that the use of a single dose of tamsulo- The incidence of clinically significant UTI, especially including fever with positive blood culture (urosepsis) requiring hospitalization of patient and IV antibacterial therapy, is significantly lower (from 0.1% to 0.7%) when comparing TPMBs with TRUS-guided biopsies. hospitalization of patient and IV antibacterial therapy, is significantly lower (from 0.1% to 0.7%) when comparing TPMBs with TRUS-guided biopsies.13 This is predominantly because, unlike with a transrectal approach, there is no needle passage through fecal flora. Grummet and colleagues performed a systematic review of the literature and found 16 series of TPMB with a total of 6609 patients where only 5 men were re-admitted to hospital for sepsis, an overall rate of just 0.076%. 32 Other studies also reflect negligible rates of sepsis, which are 40 to 70 times lower than those sin, 0.4 mg, at the time of template biopsy significantly reduced the rate of AUR, with a number needed to treat score of 13.34 The authors demonstrated that a single prophylactic dose of tamsulosin lowered the risk of AUR to 5.3% with a relative risk of developing retention without tamsulosin of 2.5.34 A large study by Pepe and colleagues reported complication rates in 3000 patients who underwent 12- versus 18- versus 24-core template transperineal biopsies.35 They showed that the risk of AUR increased from 4.1% to 7.1% and 11.1%, respectively, suggesting that the number of cores taken has a Vol. 20 No. 1 • 2018 • Reviews in Urology • 23 4170018_04_RIU0785_V1_rev03.indd 23 5/2/18 12:28 PM Complications of TRUS vs TPMB continued TABLE 4 Acute Urinary Retention After TRUS and TPMB Procedures Among Largest Series TPMB % (N) F35 Pepe P, Aragona Grummet JP et al32 Vyas L et al22 Suzuki M et al23 Muthuveloe D et al34 Mai Z et al26 Present study 6.7 (3000) 0 (1194) 1.1 (634) 0 (539) 12.5 (200) 1.9 (3007) 7.9 (379) TRUS-guided % (N) Loeb S et al (ERSPC)20 Nam RK et al19 Womble PR et al (MUSIC)36 Wagenlehner FM et al (GPIU)37 Marino K et al38 Chiang IN et al33 Present study 0.8 (10,474) 1.4 (75,190) 0.56 (4,087) 3.1 (521) 2.4 (455) 2.1 (1,875) 0 (265) ERSPC, European Randomized Study of Screening for Prostate Cancer; GPIU, Global Prevalence Study of Infections in Urology; MUSIC, Michigan Urological Surgery Improvement Collaborative; TPMB, transperineal mapping biopsy; TRUS, transrectal ultrasound–guided prostate biopsy. direct correlation with the rate of AUR. This was similar to the data in the current study, although when controlling for prostate volume, the number of cores removed was not an independent predictor of retention. Even though we did not find retention in our TRUS population, Shen and colleagues in a systematic review and meta-analysis of all randomized and case-control trials comparing TRUS with TPMB biopsy found similar rates in both groups.40 The discrepancies in retention rates in TPMB is most likely related to how the procedure is performed. When the biopsy index is greater than 1 core/cc of PV (which increases the number of punctures for larger prostates) AUR will increase. Buskirk and associates showed that there was a correlation between gland size and the likelihood of going into AUR following template biopsies.41 Subjects with a gland size of ,50 mL exhibited an AUR rate of 4%, whereas those with a gland size of .50 mL had an AUR rate of 20% (P 5 0.039). Our data suggested this threshold of PV to predict a possibility of development of AUR when patients with #42 cc (median PV size, 41.6 cc) developed AUR in 2.7% of cases versus those with larger glands as of 13.4%, an almost six-fold increase. The present study also demonstrated that two factors significantly contributed to the development of AUR: age .65 years and PV greater than 42 cc. Even though one site (UCAMC) routinely discharged patients with a catheter in place for 1 to 2 days following TPMB, this did not change the likelihood of catheter reinsertion when compared with the men who had their catheters removed in the recovery room (HH). It would be reasonable to leave a catheter for several days and or consider adding an alpha-blocker in these higher-risk patients. Prospective trials where patients can be randomized based on these factors may help better MAin POinTS • Urinary tract infections are 5.4 times more common in transrectal ultrasound (TRUS)–guided biopsy compared with transperineal mapping biopsy (TPMB). In addition, the risk of infection is 5.8 times greater in men undergoing TRUS-guided biopsy when more than 12 cores are taken, which is common with MRI-targeted biopsy procedures. Additional infection measures should be considered in men undergoing more than 12 TRUSguided biopsy cores. • In the present study, TPMB was rarely associated with infection (0.78%) but more commonly with urinary retention (7.9%). Urinary retention was associated with older age and larger prostates. Men older than 65 years and with PV greater than 42 cc are at a four- to five-times greater risk. • Consideration should be given to discharge these men with urinary catheters following the procedure. 24 • Vol. 20 No. 1 • 2018 • Reviews in Urology 4170018_04_RIU0785_V1_rev03.indd 24 5/2/18 12:28 PM Complications of TRUS vs TPMB define retention risk as well as optimal management and prophylaxis. Our data also seem to imply that catheter reinsertion is associated with an increased risk of infection, which could also be minimized with longer catheter drainage in older men with larger glands. One of the limitations of the current study was that the biopsies were performed sequentially. Ideally, a randomized prospective trial comparing TRUS with TPMB for cancer detection and morbidity would be better able to discern whether one has an advantage over the other. 3. 4. 5. 6. 7. 8. 9. Conclusions Urinary tract infections are 5.4 times more common in TRUSguided biopsy compared with TPMB. In addition, the risk of infection is 5.8 times greater in men undergoing TRUS-guided biopsy when more than 12 cores are taken, which is common with MRI-targeted biopsy procedures. Additional infection measures should be considered in men undergoing more than 12 TRUSguided biopsy cores. In the present study, TPMB was rarely associated with infection (0.78%) but more commonly with urinary retention (7.9%). Urinary retention was associated with older age and larger prostates. Men older than 65 years and with PV greater than 42 cc are at a four- to fivetimes greater risk. Consideration should be given to discharge these men with urinary catheters following the procedure. References 1. 2. United States Biopsy Procedures Outlook to 2020. Global Data website. https://www.marketresearch. com/product/sample-8288025.pdf. Accessed March 6, 2018. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017:67:7-30. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 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The results of transperineal versus transrectal prostate biopsy: a systematic review and meta-analysis. Asian J Androl. 2012;14:310-315. Buskirk SJ, Pinkstaff DM, Petrou SP, et al. Acute urinary retention after transperineal templateguided prostate biopsy. Int J Radiat Oncol Biol Phys. 2004;59:1360-1366. Vol. 20 No. 1 • 2018 • Reviews in Urology • 25 4170018_04_RIU0785_V1_rev03.indd 25 5/2/18 12:28 PM