NCCN Guidelines for Early Detection for Prostate Cancer Version 2.2021

By GU Oncology Now Editors - Last Updated: January 17, 2022

Interview with Preston Sprenkle, MD, Associate Professor in the Department of Urology, Yale School of Medicine, New Haven, CT; urology specialist at Yale Cancer Center and VA Connecticut Healthcare System

The National Comprehensive Cancer Network (NCCN) clinical practice guideline on early detection of prostate cancer is typically updated annually. During 2021, however, there have been significant changes in this area, including the utilization of multiparametric magnetic resonance imaging (mpMRI), the role of DRE in prostate cancer screening, the definition of certain groups at increased risk of prostate cancer, evaluation of germline mutations, and management of high grade prostatic intraepithelial neoplasia. To that end, after the first 2021 guideline was issued in January, a second update was deemed necessary.

GU Oncology Now spoke with Preston Sprenkle, MD, about the changes in the most recent NCCN prostate cancer, early detection guideline update (version 2.2021), issued July 14, 2021.1 Dr. Sprenkle is Associate Professor in the Department of Urology, Yale School of Medicine, New Haven, CT, and urology specialist at Yale Cancer Center and VA Connecticut Healthcare System. He is a member of the NCCN Prostate Cancer Early Detection Panel. Dr. Sprenkle spoke about the latest guideline update at the AdMeTech 5th Global Summit on Precision Diagnosis and Treatment of Prostate Cancer (virtual), held September 23-25, 2021.2

GU Oncology Now: Recommendations for PSA screening appear to be still evolving. What are the data that drive the NCCN to advise PSA screening at age 45 for average-risk patients compared with other guidelines, such as the American Urological Association (AUA),3 that recommend starting at a later age?

Dr. Preston Sprenkle: Our recommendations are based on consensus reached among panel members who include epidemiologists, urologists, medical oncologists, and patient advocates. Starting screening at age 45 is largely based on the recommendations of the epidemiologists in the group who presented their studies. There is a significant benefit to early PSA testing. The guideline shows a breakdown for different repeat evaluation time points based on the initial PSA measurement. Studies out of Memorial Sloan-Kettering Cancer Center Fred Hutchinson Cancer Research Center, and large Swedish databases have demonstrated convincingly that a PSA below the age-based mean correlates with a low likelihood of significant morbidity or even mortality from prostate cancer over a lifetime.4-8 The reason to go to age 45 is because finding those men who have a high PSA at that time will identify high-risk men early, when you can potentially treat them prior to metastasis. It’s not huge number, but it’s a reasonable number of men. It doesn’t mean that everyone should be getting annual PSA testing starting at age 45, however. It means you get one test. If you’re below the median, you may not need another test for five years. But if someone has an elevated PSA, say >4 ng/ mL, then they should have a biopsy, or if the PSA is trending up, they should be followed more closely. One change in the latest guideline involves substituting the term “African ancestry” for “African American.”

GU Oncology Now: What was the reason for that?

Dr. Preston Sprenkle: The language regarding African ancestry was changed to be more inclusive because we are learning that there are multiple factors including ancestry and germline mutations, not just BRCA mutations. There was a lot of discussion about that change in our most recent meeting; we decided the term “African ancestry” is the most appropriate. That’s probably going to change in the next guideline, but, again, the goal is to be appropriately inclusive and descriptive and not exclude populations that really should be considered in those risk groups.

GU Oncology Now: Do you ever test for germline mutations in your patients?

Dr. Preston Sprenkle: That is also controversial, and a discussion point among the panel was whether we should recommend this as standard of care. We decided that we couldn’t recommend it because it’s expensive – it’s not covered by insurance – and we don’t know what to do with a large part of the information. So at this point, we are not advocating that everyone be screened for this. What we are trying to communicate is that men with identified high-risk features like African ancestry, strong family history of prostate cancer, or a known mutation associated with higher risk or higher-grade prostate cancer should consider earlier screening than those who would typically be screened at age 45.

GU Oncology Now: You mentioned in your AdMeTech talk that the DRE is no longer mandatory. Can you tell us more about that?

Dr. Preston Sprenkle: This is also exceptionally controversial. We reviewed the published data and there are several studies and reviews that have shown limited benefit in detecting prostate cancer with DRE alone. Proponents of DRE would say that there are some cancers that do not produce PSA and can only be found with an abnormal DRE, and they are correct. It really depends on what your risk tolerance is from a population standpoint. Several panel members were adamant in not removing the DRE as part of the evaluation for prostate cancer, because they felt strongly that we should not miss the very rare high-grade disease.

They are not wrong, but it doesn’t necessarily mean that a DRE must be a part of the standard of care for prostate cancer screening in the primary care setting if they’re also getting a PSA.

GU Oncology Now: So you’re keeping it in the guidelines, but with flexibility?

Dr. Preston Sprenkle: Right. It’s meant to be flexible because many people read these guidelines and use them as a literal guide to how they should practice. As urologists, we do perform DREs on almost all our patients, but not only urologists read these guidelines.

GU Oncology Now: One of the exciting changes to this guideline is to make mpMRI part of standard of care. Where does it fit and are there any exceptions to this recommendation?

Dr. Preston Sprenkle: This change has been coming for years. We’ve been reviewing the data on MRI-targeted biopsy. Since we added MRI as an option, each year, we’ve felt more comfortable strengthening the language about its importance. A 2019 Cochrane review did a great job summarizing the data and demonstrating clearly how important mpMRI is in both a biopsy-naive setting as well as in someone with a negative prostate biopsy.9 To answer your question, if there is an MRI available, I’m not sure there would be any reason not to get an MRI.

GU Oncology Now: Can you give us an idea of what changes you foresee in the next version of the guideline?

Dr. Preston Sprenkle: I can tell you that we have seen a lot of studies of new products that might be included in the guideline. There are many urine and serum markers to help assess prostate cancer risk. The ones in the current guideline include 4Kcore, prostate health index (PHI), PSA density (PSAD), SelectMDx, and ExoDx prostate test (EPI). These are modifiers that help assess risk. There are many other similar products, and we are reviewing data on these. There are also emerging imaging modalities and growing evidence in the world of genomics and genetics. There is interest in transperineal biopsy and the decreased risk of infection versus transrectal biopsy, but there is additional cost associated with using transperineal biopsy devices.10 The devices are disposable and most of these biopsies need to be done under general anesthesia.11

So it’s important to understand that the guidelines are made not only with the science in mind, but also considering cost and financial toxicity. It is. Financial toxicity is a big consideration because insurers and insurance companies look at guidelines to determine what they will cover. We want to have the appropriate treatments available for our patients, but we try to be judicious in not recommending anything that might not be necessary.

David Ambinder, MD is a urology resident at New York Medical College/Westchester Medical Center. His interests include surgical education, GU oncology and advancements in technology in urology. A significant portion of his research has been focused on litigation in urology.


  1. Carroll PR (chair), Parsons JK (vice-chair); National Comprehensive Cancer Network (NCCN) Prostate Cancer Early Detection Panel. NCCN Clinical Practice Guidelines in Oncology: Prostate cancer early detection. Version 1,2022. July 2021. Available at
  2. Sprenkle PC. Updates of changes in the early detection of prostate cancer NCCN guidelines 2021. Presentations from the 5th Global Summit on Precision Diagnosis and Treatment of Prostate Cancer. Grand Rounds in Urology. Available at presentations-from-the-5th-global-summit-on-precision-diagnosis/
  3. Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA guideline. American Urological Association. Published 2013; Reviewed and validity confirmed 2018. Available at Dectection-of-Prostate-Cancer-JU.pdf
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  9. Drost FH, Osses DF, Nieboer D, et al. Prostate MRI, with or without MRI‐targeted biopsy, and systematic biopsy for detecting prostate cancer. Cochrane Database Syst Rev. 2019;4(4):CD012663. DOI: 10.1002/14651858.CD012663.pub2
  10. Pradere B, Veeratterapillay R, Dimitropoulos K, et al. Nonantibiotic strategies for the prevention of infectious complications following prostate biopsy: a systematic review and meta-analysis, J Urol. 2021;205(3):653-663. DOI: 10.1097/JU.0000000000001399
  11. Alltok M, Kim B, Patel BB, et al. Cost and efficacy comparison of five prostate biopsy modalities: a platform for integrating cost into novel-platform comparative research. Prostate Cancer Prostatic Dis. 2018;21(4):524-532. DOI: 10.1038/s41391-018-0056-7