PROSTATE CANCER Early Detection of Prostate Cancer: Highlights From 2023 AUA/Society of Urologic Oncology Guidelines
By: Udit Singhal, MD, University of Michigan, Ann Arbor, Mayo Clinic, Rochester, Minnesota; Daniel A. Barocas, MD, MPH, FACS, Vanderbilt University Medical Center, Nashville, Tennessee; Simpa S. Salami, MD, MPH, University of Michigan, Ann Arbor | Posted on: 07 Sep 2023
Given continued advances in prostate cancer early detection—from imaging to diagnostic approaches used for risk stratification—updates to the existing framework to guide clinical decision-making were needed. The AUA and Society of Urologic Oncology (SUO) issued new guidelines published in The Journal of Urology® in July 2023, with a specific focus on these domains.1,2 The new guidelines statements are based on the expert panel’s interpretation of a comprehensive systematic review of the existing literature, with the stated goal of identifying clinically significant cancer while minimizing harms. Below, we provide a synopsis of notable changes in the new guidelines compared to those previously published in 2013.3
Part I: Screening
In contrast to a purely age-based approach to PSA-based screening as recommended in the 2013 guideline, the current version emphasizes the importance of shared decision-making for all patients in whom screening would be appropriate. Further, given additional results from long-term follow-up of the European Randomized Study of Screening for Prostate Cancer and Göteborg randomized prostate cancer screening trials showing a mortality benefit to PSA-based screening and limited data suggesting utility of other biomarkers or imaging as first-line tests, PSA is still recommended as the first screening test.4,5
In those at average risk, it is now stated that PSA testing can be offered starting at age 45, compared to the initial recommendation in 2013 against routine screening in men 40-54 years. While the 2013 guidelines recommended an individualized approach to PSA testing in patients aged 40-54 years with high risk factors (Black race, strong family history), this statement was amended to include a strong recommendation for screening beginning at 40-45 years for this population. Patients with germline mutations in BRCA2 or mismatch repair genes (MSH2, MSH6) were also recommended to undergo early screening because of high risk for detection of aggressive tumors.6,7 With regard to frequency of screening, the updated guidelines recommend screening every 2 to 4 years for patients aged 50-69 years, with potential for personalization based on shared decision-making.
Digital rectal exam (DRE) is now considered optional as a complementary screening modality to PSA testing. Results from the PROBASE trial of over 40,000 men showed a low rate of cancer detection using DRE with delayed PSA testing.8 However, in the setting of elevated PSA ≥2 ng/mL, the guidelines state clinicians should strongly consider DRE to establish the risk of clinically significant cancer. Lastly, the new guidelines also include a statement suggesting risk calculators may be used to aid in shared decision-making, with the caveat that these tools have substantial variability with wide population-based averages and uneven calibration.
Part II: Considerations for Prostate Biopsy
Due to the widespread availability and utility of prostate multiparametric MRI (mpMRI) in modern management algorithms, the new guidelines recommend a defined role for mpMRI. Based on results from the PRECISION study showing increased detection of clinically significant cancer with reduced detection of clinically insignificant disease with MRI-targeted vs systematic biopsy, the panel provided a conditional recommendation for prebiopsy mpMRI.9 Additional randomized trial results have suggested noninferiority of an MRI-targeted biopsy-only approach to screening for prostate cancer.10,11 However, in those with negative mpMRI results and elevated risk, systematic biopsy is still recommended because of the risk of missing clinically significant cancers with negative MRI alone.12 In those with suspicious lesions on mpMRI, it is recommended that targeted biopsy be performed. However, the role of the addition of systematic biopsy in this setting is debatable, with the tradeoff being increased detection of low-risk cancers vs missed clinically significant cancers without systematic biopsy.11,13
The guidelines also address the numerous serum-, urine-, and tissue-based biomarkers available for identifying patients for prostate biopsy. However, they are recommended only in scenarios in which test results would influence decision-making regarding need for biopsy. While various biomarkers have documented utility in this setting and ability to reduce unnecessary biopsies, no specific biomarker is endorsed as no comparative studies are available. Nonetheless, these tools are available for use in the initial and repeat biopsy settings (see Figure). In the setting of a prior negative biopsy, the panel recommends use of a risk assessment approach that combines patient factors, PSA, mpMRI results, and biomarker tests as needed for reevaluation.
With regard to biopsy technique, the panel recommends either a transrectal or transperineal approach, citing similar cancer detection rates with both techniques. While some evidence suggests superior safety of transperineal biopsy14,15 along with improved clinically significant cancer detection when using a targeted transperineal approach, the panel did not recommend preferential use of the transperineal technique as the data are still mixed.16,17
Key Differences From the European Association of Urology and National Comprehensive Cancer Network Guidelines
Both the European Association of Urology (EAU) guidelines18 and the National Comprehensive Cancer Network (NCCN) guidelines19 still recommend performing DRE in addition to PSA for screening. Despite the low sensitivity and specificity of DRE, the EAU guidelines state, “Men requesting an early diagnosis should be given a PSA test and undergo a DRE,” as in 18% of cases prostate cancer is detected by suspect DRE alone, and an elevated PSA with abnormal DRE doubles the risk of positive prostate biopsy.20 While the AUA/SUO guidelines state that mpMRI may be used prior to initial biopsy, this is the recommended practice by the EAU and NCCN guidelines, with a “strong” strength rating. This is complemented with the recommendation by the EAU that prostate biopsy can be omitted in patients with negative mpMRI, albeit this was given a “weak” strength rating. In this scenario, AUA/SUO guidelines recommend proceeding with a systematic biopsy in those with elevated risk, and the NCCN cautions that significant cancers can exist outside of MRI-identified targets. EAU guidelines also recommend performing targeted biopsy only with a positive mpMRI (Prostate Imaging Reporting & Data System 3 or higher) result, whereas AUA/SUO and NCCN guidelines state that systematic biopsy also may be considered and is preferred. Given studies showing improved detection of clinically significant cancer and reduction in infectious complications with targeted transperineal biopsy, EAU guidelines recommend a transperineal over transrectal approach. However, the NCCN states transrectal or transperineal approaches can be used.
Future iterations of these guidelines will seek to address other evolving areas in prostate cancer detection to assist clinicians. For example, the panel will evaluate forthcoming studies on comparative effectiveness of different biomarkers and their sequencing with other clinical tools, such as mpMRI, to make recommendations about using the appropriate biomarker for each clinical scenario. Further, recommendations regarding utility of prostate-specific membrane antigen positron emission tomography/CT imaging and specialized recommendations for diverse patient populations are needed. Nonetheless, the update by the AUA/SUO was a needed renewal given the evolving landscape of prostate cancer screening and early detection.
- Wei JT, Barocas D, Carlsson S, et al. Early detection of prostate cancer: AUA/SUO guideline part I: prostate cancer screening. J Urol. 2023;210(1):46-53.
- Wei JT, Barocas D, Carlsson S, et al. Early detection of prostate cancer: AUA/SUO guideline part II: considerations for a prostate biopsy. J Urol. 2023;210(1):54-63.
- Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA guideline. J Urol. 2013;190(2):419-426.
- Hugosson J, Roobol MJ, Månsson M, et al. A 16-yr follow-up of the european randomized study of screening for prostate cancer. Eur Urol. 2019;76(1):43-51.
- Maria F, Marianne M, Arnsrud GR, et al. Results from 22 years of followup in the Göteborg randomized population-based prostate cancer screening trial. J Urol. 2022;208(2):292-300.
- Page EC, Bancroft EK, Brook MN, et al. Interim results from the IMPACT study: evidence for prostate-specific antigen screening in BRCA2 mutation carriers. Eur Urol. 2019;76(6):831-842.
- Bancroft EK, Page EC, Brook MN, et al. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study. Lancet Oncol. 2021;22(11):1618-1631.
- Arsov C, Albers P, Herkommer K, et al. A randomized trial of risk-adapted screening for prostate cancer in young men—results of the first screening round of the PROBASE trial. Int J Cancer. 2022;150(11):1861-1869.
- Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018;378(19):1767-1777.
- Eklund M, Jäderling F, Discacciati A, et al. MRI-targeted or standard biopsy in prostate cancer screening. N Engl J Med. 2021;385(10):908-920.
- Hugosson J, Månsson M, Wallström J, et al. Prostate cancer screening with PSA and MRI followed by targeted biopsy only. N Engl J Med. 2022;387(23):2126-2137.
- Sathianathen NJ, Omer A, Harriss E, et al. Negative predictive value of multiparametric magnetic resonance imaging in the detection of clinically significant prostate cancer in the prostate imaging reporting and data system era: a systematic review and meta-analysis. Eur Urol. 2020;78(3):402-414.
- Ahdoot M, Wilbur AR, Reese SE, et al. MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis. N Engl J Med. 2020;382(10):917-928.
- Jacewicz M, Günzel K, Rud E, et al. Antibiotic prophylaxis versus no antibiotic prophylaxis in transperineal prostate biopsies (NORAPP): a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2022;22(10):1465-1471.
- Daniele C, Maria PG, Terence LYX, et al. Infection rate after transperineal prostate biopsy with and without prophylactic antibiotics: results from a systematic review and meta-analysis of comparative studies. J Urol. 2022;207:25-34.
- Tu X, Liu Z, Chang T, et al. 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.
- Fabio Z, Giancarlo M, Veeru K, et al. The detection of prostate cancer with magnetic resonance imaging-targeted prostate biopsies is superior with the transperineal vs the transrectal approach. A European Association of Urology-Young Academic Urologists Prostate Cancer Working Group multi-institutional study. J Urol. 2022;208(4):830-837.
- Mottet N, Cornford P, van der Bergh RCN, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. 2022. Accessed April 13, 2022. https://uroweb.org/guidelines/prostate-cancer
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer Early Detection. Version 1.2023. https://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf
- Gosselaar C, Roobol MJ, Roemeling S, et al. The role of the digital rectal examination in subsequent screening visits in the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam. Eur Urol. 2008;54(3):581-588.