The advent of transrectal (TR) ultrasound resulted in a dramatic shift in the late 1980s as urologists transitioned from finger-directed prostate biopsies to ultrasound (US)- guided biopsies.1 Initially, biopsies were conducted using a 6-core biopsy template, which was soon expanded to 12 cores in conjunction with patients undergoing routine screening for prostate-specific antigen (PSA).2 Although mortality from the disease is not common, it is estimated that 35,000 males will experience prostate cancerrelated mortality in 2022.3 Furthermore, approximately 270,000 men are expected to receive a new diagnosis of prostate cancer each year. According to data from 2013, an estimated ~1.3 million diagnostic biopsies are performed in the United States annually to establish these diagnoses.1,4
In this article, we will discuss the complications of modern prostate biopsy techniques and explore upcoming alternatives for establishing a prostate cancer diagnosis. Most prostate biopsies conducted are done via the TR route under local or general anesthesia; however, there has been growing interest in utilizing the transperineal (TP) route due to its beneficial impact on rates of infection. A large-scale meta-analysis comparing TR with TP biopsies found equivalent diagnostic yield, rates of gross hematuria, and urinary retention for the 2 modalities.5 Patients who received TR biopsies were at higher risk for developing systemic inflammatory response syndrome (SIRS) suspicious for systemic infection as well as higher rates of rectal bleeding.5 By comparison, patients who had TP biopsies had much lower rates of SIRS and minimal rectal bleeding; however, they had significantly higher rates of perineal discomfort and pain.5
Multiple steps are often required to prepare patients for a TR prostate biopsy. Although use of an enema for bowel preparation does not affect diagnostic accuracy, the resulting lower stool burden in the rectal vault may assist the urologist in performing a timelier and more accurate biopsy. The American Urological Association (AUA) guidelines recommend antimicrobial prophylaxis prior to TR biopsy using a combination of first-, second-, or third-generation cephalosporin plus aminoglycoside or, alternatively, a fluroquinolone.6 In patients with contraindications for either regimen, use of aztreonam (Cayston®) should be considered.6 Patients undergoing TR prostate biopsy without general anesthesia commonly receive a local anesthetic through injection of a prostatic block (eg, lidocaine). The most frequent approach involves injecting 5 mL of anesthetic at the junction of the seminal vesicle and the base of the prostate under transrectal ultrasound (TRUS) guidance.
Systematic TR prostate biopsy involves obtaining a total of 12 cores; these samples are drawn primarily from the peripheral zone, with some also drawn from the lateral and medial components of the prostate. Most guidelines recommend focusing on the lateral aspects of the prostate as well as the apex to maximize the amount of prostatic peripheral zone that can be sampled.7 Additional topics of interest include lesion-specific biopsies directed at concerning areas noted on multiparametric prostate MRI (mpMRI) and abnormal nodules detected through digital rectal examination.
There are 2 primary ways in which mpMRI of the prostate is used to detect clinically significant prostate cancer. After the radiologist provides a 3-dimensional map of clinically suspicious lesions graded using the American College of Radiology’s PI-RADS® (Prostate Imaging Reporting & Data System®) system, the urologist can perform a targeted biopsy in 1 of 2 ways: In a fusion-based biopsy system (either TR or TP), the fusion magnetic resonance imaging (MRI) image is aligned to the live TRUS images to allow simultaneous tracking of the suspicious lesions. The biopsies can then be performed using a combination of TRUS and MRI guidance.
Alternatively, if a fusion system is unavailable, the urologist can perform a “cognitive” biopsy. In this case, the 3-dimensional location of the suspicious lesion on MRI is found on US using cognition, after which it is biopsied. The most commonly utilized fusion systems are UroNav (Philips) and Artemis with ProFuse (innoMedicus).1 Currently, no significant evidence exists to suggest that MRI/US fusion techniques are superior to cognition-based techniques.7 Currently, for patients who have not received any prior prostate biopsy, all major guidelines recommend combining use of mpMRI-directed prostate biopsy in conjunction with a systematic prostate biopsy.7
What about the TP technique? Apart from the reduced rate of infectious episodes mentioned earlier, other potential benefits include serving as a modality for biopsy in patients without rectal access, or in those suspected to have tumors in the prostatic apex, which may not be easily accessed via the TR route.1 The diagnostic accuracy of the TP route is also reported to be superior. In a meta-analysis conducted by Tu et al, 315 patients undergoing TR MRI fusion biopsy were compared with 328 patients undergoing TP MRI fusion biopsies. The pooled diagnostic sensitivity was higher for the TP arm (86%) than the TR arm (73%).8 The primary downsides of the TP approach are logistical. Due to the positioning required (dorsal lithotomy), as well as the uncomfortable nature of placing needles through the perineum, most patients will require some level of anesthetic support.1
Despite the many advances in prostate biopsy, including a rapid transition to implementation of TP biopsy as recommended by the most recent urology guidelines,7 there is still tremendous interest in noninvasive testing modalities to establish a diagnosis of prostate cancer. Benefits of noninvasive modalities include the ability to perform active surveillance with less morbidity and less utilization of resources such as hospital visits or operating room time. Additionally, such modalities can be used to monitor disease status (ie, recurrence) or response to treatment. One such modality is liquid prostate biopsy (analyzing body fluids such as urine or blood) employing underlying technology to analyze circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating RNA, or even extracellular vesicles.9
The basic concept behind CTCs involves detection of blood-borne cancer cells that are released into the circulation by the primary tumor or metastatic tumors. The primary limitation of CTC technologies is the rarity of such cells within the systemic circulation, with an estimate of ~1 tumor cell per 1 billion cells.9 In contrast to CTCs, cfDNA focuses on detection of nucleic acids released during apoptosis of cancer cells. Many of these DNA strands carry mutational segments specific to the tumor of interest. CTC utilization in the localized prostate cancer setting is relatively uncharacterized primarily owing to the widespread utilization of PSA.9
Despite limited data focusing on utility for patients with localized prostate cancer, some interesting projects were presented at the AUA’s 2022 annual meeting. A recently available urine-based liquid biopsy tool called miR Sentinel™ (miR Scientific) shows promise. The liquid biopsy uses noncoding RNAs isolated from the urinary exosome of patients thought to have prostate cancer. One presentation at AUA 2022 discussed a series of 763 biopsy-naive patients with prostate cancer undergoing biopsy for diagnosis. When compared to results from miR Sentinel, the liquid biopsy had 92.2% sensitivity and predicted clinically significant prostate cancer in 93% of cases.10
Overall, continued research and development into liquid biopsy technologies will likely enable greater access to prostate cancer while simultaneously offering the ability to decrease cost and decrease the morbidity of prostate cancer diagnosis through prostate biopsy.
- Partin AW, Dmochowski RR, Kavoussi LR, Peters CA, Wein A, eds. Campbell-Walsh-Wein Urology, 12th ed. Philadelphia: Elsevier; 2020. https://www.elsevier.com/books/campbell-walsh-urology/partin/978-0-323-67227-6
- Hodge KK, McNeal JE, Terris MK, Stamey TA. Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J Urol. 1989 Jul;142(1):71-4; discussion 74-5. doi: 10.1016/s0022-5347(17)38664-0
- National Cancer Institute, Surveillance, Epidemiology and End Results Program (SEER). Cancer Stat Facts: Prostate Cancer. Accessed August 18, 2022. https://seer.cancer.gov/statfacts/html/prost.html
- Aubry W, Lieberthal R, Willis A, Bagley G, Willis SM III, Layton A. Budget impact model: epigenetic assay can help avoid unnecessary repeated prostate biopsies and reduce healthcare spending. Am Health Drug Benefits. 2013;6(1):15-24. PMCID: PMC4031702
- Xiang J, Yan H, Li J, Wang X, Chen H, Zheng X. Transperineal versus transrectal prostate biopsy in the diagnosis of prostate cancer: a systematic review and meta-analysis. World J Surg Oncol. 2019;17(1):31. doi: 10.1186/s12957-019-1573-0.
- Wolf JS Jr. Antimicrobial prophylaxis for transrectal prostate biopsy: organizational recommendations. Accessed August 23, 2022. https://www.auanet.org/documents/ practices-resources/quality/quality-improvement-summit/2014/Stuart-Wolf-Antibiotic-Choices-Guidelines.pdf
- European Association of Urology Guidelines: Prostate Cancer. Edition presented at the EAU Annual Congress Amsterdam 2022. Accessed August 23, 2022. https://uroweb.org/guidelines/prostate-cancer
- Tu X, Liu Z, Chang T, Qiu S, Xu H, Bao Y, Yang L, Wei Q. Transperineal magnetic resonance imaging-targeted biopsy may perform better than transrectal route in the detection of clinically significant prostate cancer: systematic review and meta-analysis. Clin Genitourin Cancer. 2019;17(5):e860-e870. doi: 10.1016/j.clgc.2019.05.006
- Lu YT, Delijani K, Mecum A, Goldkorn A. Current status of liquid biopsies for the detection and management of prostate cancer. Cancer Manag Res. 2019;11:5271-5291. doi: 10.2147/ CMAR.S170380
- Klotz L, Wang W, Lopez Pujals A, et al. A urinary exosome assay interrogating small non-coding RNAs accurately identifies and stratifies prostate cancer into low-intermediate-or high-risk disease. J Urol. 2022;207(suppl 5):e194. Abstract PD11-11. doi: 10.1097/ JU.0000000000002537.11
Centers for Disease Control and Prevention. Cancer Statistics At a Glance. Accessed August 18, 2022. https://gis.cdc.gov/Cancer/USCS/#/AtAGlance/
National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Prostate Cancer. Version 4.2022. Accessed August 18, 2022. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
Taneja SS, Bjurlin MA, Carter HB, et al; Prostate Biopsy Specimen Workgroup; AUA Staff. AUA/Optimal Techniques of Prostate Biopsy and Specimen Handling [white paper]. Accessed August 23, 2022. https://www.auanet.org/documents/education/clinical-guidance/prostate-biopsy-whitepaper.pdf