The role of PSA density in the MRI pathway for prostate cancer diagnostics

Download PDF Editorial Open access Published: 26 July 2022 The role of PSA density in the MRI pathway for prostate cancer diagnostics Hannes Cash  ORCID: orcid.org/0000-0002-1064-56331,2 &

Martin Schostak1  Prostate Cancer and Prostatic Diseases volume 26, pages 437–438 (2023)Cite this article

4030 Accesses

3 Citations

4 Altmetric

Metrics details

Subjects Cancer screeningOutcomes research A Correction to this article was published on 03 April 2023

This article has been updated

After initial resistance, the urological community has embraced the multiparametric MRI (mpMRI) within the diagnostic pathway of prostate cancer (PCa) [1]. Overall, this had led to a reduced

number of men undergoing prostate biopsy and the detection rates for the men who do undergo targeted biopsy after a positive mpMRI (≥PI-RADS 3) are higher compared to systematic (Precision

trial) [2]. Looking beyond the improvements of the MRI pathway, the detection rate for clinically significant PCa (csPCa), defined as ISUP Grade Group (GG) 2, is around 38–40% overall

[2,3,4]. This seems rather low and is mostly driven by the low detection rate for PI-RADS 3 lesion (12% in the PRECISION trial compared to 60 and 83% for PI-RADS4/5) [2]. Therefore there is

evident room for further improvement.

In this issue of Prostate Cancer and Prostatic disease Friesbie et al. show that PSA density (PSAd) is complementary to PI-RADS in detecting csPCa [5]. The study retrospectively included 327

men with 709 lesions who underwent both targeted and systematic biopsy. For the analysis, only the targeted biopsies (2 cores per lesion/mean of 4.3 cores per patient) were included to

evaluate PSAd in a targeted only setting. The overall detection rate for csPCa in the cohort was 25 and 42% for all PCa. On a per patient analysis, a PSAd cuttof of ≥0.1 ng/ml/cc improved

csPCa detection by 7% for PI-RADS 3, 17% for PI-RADS 4 and 15% for PI-RADS 5. The author did not present or discuss the benefits and risk of omitting biopsies and missed cancers according to

their suggested risk stratification. The IMRIE study which retrospectively analyzed 2642 men showed that adding the standard PSAd (≥0.15 ng/ml/cc) to the MRI-pathway increased sensitivity

and negative predictive value (NPV) for GG ≥ 2 (87.3–96.6% and 87.5–90.6%) [6]. Using a PSA density 0.12 ng/ml/ml improved sensitivity and NPV even further [6].

The novelty of the study of Friesbie et al. is that their analysis is based on a targeted-only approach, a concept gaining supporters. Although, currently the PI-RADS steering committee

suggests a target saturation rather than a 2 core per lesion approach when performing targeted only biopsy. Further the authors explored an improved PSAd cutoff of ≥0.1 ng/ml/cc which lead

to similar biopsy results for PI-RADS 3 with PSAd ≥0.1 ng/ml/cc compared to PI-RADS 4. The optimal PSAd threshold should therefore be further investigated to challenge the current PSAd of

≥0.15 ng/ml/cc in men undergoing targeted biopsy. First studies already evaluated the impact of different biopsy strategies according to PI-RADS/Likert and different PSAd cut-offs on omitted

biopsies, missed GG 1 PCa and csPCA (i.e., I-RADS 4-5 or PI-RADS 3 if PSAd >0.10 or PSAd >0.2), 27% omitted biopsies, 24.4% missed GGG 1 and 4% missed csPCa) [7].

The clinical implications of this study by Friesbie et al. are that PSAd should be included when counseling men prior to targeted biopsy and may also be valid in a targeted-only setting.

Depending on the biopsy strategy used (targeted only vs. combined), a PSAd cutoff ≥0.15 ng/ml/cc can already reduce the number of men with PI-RADS 3 lesions to undergo biopsy [8]. Why is

PI-RADS 3 so critical? First, the detection rate remains low and many men still undergo unnecessary biopsies. Second, depending on the radiologist’s experience the number of lesions rated

PI-RADS 3 may vary depending on reader experience, even in the Academic setting which are the basis of most published data. This phenomenon probably is even greater in the community setting.

In the PRECISION trial, the central MRI re-reading reduced the rate of PI-RADS 3 reading from 21 to 5% with a shift towards PI-RADS 1/2 compared to all sites [2]. Until artificial

intelligence may standardize mpMRI reading even further, adding a simple and readily available clinical measure such as PSA density has the potential to reduce the number on men undergoing

biopsy while increasing the rate of csPCa [9]. Initial studies also show benefits for adding PSAd into the decision process for repeat biopsy during Active Surveillance or during follow-up

for men with a negative targeted biopsy [10, 11]. Variability of prostate volume measurement (MRI vs. TRUS) should be considered. Overall, the PSAd is ready at hand and does not involve

further tests, we feel that PSAd is under-utilized in daily practice. The same under-utilization also applies to the available risk calculators, which already include PSA and prostate

volume. The ERSPC-MRI calculator was recently tested in the study cohort of the PRECISION trial and showed that 13% of MRI scan would have been avoided, missing 7% csPCa and targeted

biopsies reduced further by 9% missing one csPCa in the MRI arm [12]. Although the MRI pathway is leading toward precision medicine and risk stratification tools make personalized

decision-making possible, the rate of missed csPCa that is acceptable remains debatable. Currently, we are caught in the dichotomy of either reducing the number men undergoing

imaging/biopsies further and optimizing the rate of detected csPCa.

A Correction to this paper has been published: https://doi.org/10.1038/s41391-023-00664-4

References Mottet N, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, et al. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer-2020 update. part 1: screening,

diagnosis, and local treatment with curative intent. Eur Urol. 2021;79:243–62. https://doi.org/10.1016/j.eururo.2020.09.042.

Article  CAS  PubMed  Google Scholar 

Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH.PRECISION Study Group Collaborators et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N

Engl J Med. 2018;378:1767–77. https://doi.org/10.1056/NEJMoa1801993.

Article  PubMed  PubMed Central  Google Scholar 

Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK.PROMIS study group et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a

paired validating confirmatory study. Lancet. 2017;389:815–22. https://doi.org/10.1016/S0140-6736(16)32401-1.

Article  PubMed  Google Scholar 

Rouvière O, Puech P, Renard-Penna R, Claudon M, Roy C, Mège-Lechevallier F.MRI-FIRST Investigators et al. Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI

in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study. Lancet Oncol. 2019;20:100–9. https://doi.org/10.1016/S1470-2045(18)30569-2.

Article  PubMed  Google Scholar 

Frisbie JW, Van Besien AJ, Lee A, Xu L, Wang S, Choksi A et al. PSA density is complementary to prostate MP-MRI PI-RADS scoring system for risk stratification of clinically significant

prostate cancer. Prostate Cancer Prostatic Dis. 2022. https://doi.org/10.1038/s41391-022-00549-y.

Stonier T, Simson N, Shah T, Lobo N, Amer T, Lee SM, et al. The “Is mpMRI Enough” or IMRIE Study: a multicentre evaluation of prebiopsy multiparametric magnetic resonance imaging compared

with biopsy. Eur Urol Focus. 2021;7:1027–34. https://doi.org/10.1016/j.euf.2020.09.012.

Article  PubMed  Google Scholar 

Falagario UG, Jambor I, Lantz A, Ettala O, Stabile A, Taimen P, et al. Combined use of prostate-specific antigen density and magnetic resonance imaging for prostate biopsy decision planning:

a retrospective multi-institutional study using the prostate magnetic resonance imaging outcome database (PROMOD). Eur Urol Oncol. 2021;4:971–9. https://doi.org/10.1016/j.euo.2020.08.014.

Article  PubMed  Google Scholar 

Rico L, Blas L, Vitagliano G, Contreras P, Rios Pita H, Ameri C. PI-RADS 3 lesions: does the association of the lesion volume with the prostate-specific antigen density matter in the

diagnosis of clinically significant prostate cancer? Urol Oncol. 2021;39:431.e9–431.e13. https://doi.org/10.1016/j.urolonc.2020.11.010.

Article  CAS  PubMed  Google Scholar 

Deniffel D, Healy GM, Dong X, Ghai S, Salinas-Miranda E, Fleshner N, et al. Avoiding unnecessary biopsy: MRI-based risk models versus a PI-RADS and PSA density strategy for clinically

significant prostate cancer. Radiology. 2021;300:369–79. https://doi.org/10.1148/radiol.2021204112.

Article  PubMed  Google Scholar 

Stavrinides V, Papageorgiou G, Danks D, Giganti F, Pashayan N, Trock B, et al. Mapping PSA density to outcome of MRI-based active surveillance for prostate cancer through joint

longitudinal-survival models. Prostate Cancer Prostatic Dis. 2021;24:1028–31. https://doi.org/10.1038/s41391-021-00373-w.

Article  PubMed  PubMed Central  Google Scholar 

Barletta F, Stabile A, Mazzone E, Brembilla G, Sorce G, Pellegrino F, et al. How to optimize follow-up in patients with a suspicious multiparametric MRI and a subsequent negative targeted

prostate biopsy. Results from a large, single-institution series. Urol Oncol. 2022;40:103.e17–103.e24. https://doi.org/10.1016/j.urolonc.2021.09.015.

Article  PubMed  Google Scholar 

Remmers S, Kasivisvanathan V, Verbeek JFM, Moore CM, Roobol MJ, ERSPC Rotterdam Study Group PRECISION Investigators Group. Reducing biopsies and magnetic resonance imaging scans during the

diagnostic pathway of prostate cancer: applying the Rotterdam prostate cancer risk calculator to the PRECISION trial data. Eur Urol Open Sci. 2021;36:1–8.

https://doi.org/10.1016/j.euros.2021.11.002.

Article  PubMed  PubMed Central  Google Scholar 

Download references

Author informationAuthors and Affiliations Department of Urology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany

Hannes Cash & Martin Schostak

PROURO, Berlin, Germany

Hannes Cash

AuthorsHannes CashView author publications You can also search for this author inPubMed Google Scholar

Martin SchostakView author publications You can also search for this author inPubMed Google Scholar

Corresponding author Correspondence to Hannes Cash.

The authors declare no competing interests.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised due to a retrospective Open Access order.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or

format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or

other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in

the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the

copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this articleCite this article Cash, H., Schostak, M. The role of PSA density in the MRI pathway for prostate cancer diagnostics. Prostate Cancer Prostatic Dis 26, 437–438 (2023).

https://doi.org/10.1038/s41391-022-00579-6

Download citation

Received: 16 May 2022

Revised: 29 June 2022

Accepted: 12 July 2022

Published: 26 July 2022

Issue Date: September 2023

DOI: https://doi.org/10.1038/s41391-022-00579-6

Share this article Anyone you share the following link with will be able to read this content:

Get shareable link Sorry, a shareable link is not currently available for this article.

Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative