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. 2023 Nov 14;309(2):e231177. doi: 10.1148/radiol.231177

Prebiopsy Risk Calculators, Such as MRI and Prostate Cancer Screening, Are Early-phase Clinical Trials

Takeshi Takahashi 1,✉
PMCID: PMC10698497  PMID: 37962502

Editor:

In the May 2023 issue of Radiology, Dr Yilmaz and colleagues (1) conclude that the next phase of clinical trials is needed for the Prostate Imaging Reporting and Data System (PI-RADS), which they suggest is capable of detecting clinically insignificant cancers in prostate-specific antigen (PSA) screening.

Both PI-RADS and MRI are considered to be prebiopsy risk calculators, addressed in Key Question 5 of the U.S. Preventive Services Task Force systematic review (2,3). They concluded that further research was needed to elucidate whether the use of adjunctive tests would improve the balance of benefits and harms of PSA screening (2,3).

The study by Dr Yilmaz and colleagues and the many studies regarding MRI are all phase 2 clinical trials. They are case series with no control group, and the end points are clinically significant cancers with pathologically predicted progression, not observed clinical symptoms. To use PI-RADS in clinical decision-making, its predictive accuracy must be tested and, conversely, whether avoidance of aggressive treatment in clinically insignificant cancers results in worse cancer mortality must also be tested. Ultimately, phase 4 (randomized controlled) trials should be conducted to provide evidence of improvement in cancer and overall mortality, which significantly reverse the balance of benefits and harms in PSA screening. However, before designing such a large trial, one should ensure that promising results have been obtained in phase 3 (case-control) trials with an appropriate control group with cancer mortality or overall mortality as the end point. Of the many prebiopsy risk calculators, including MRI, none have undergone such trials (3,4).

In addition, the U.S. Preventive Services Task Force issued a grade C recommendation for PSA screening (2,3). By definition, grade C means that there is insufficient evidence that the benefits outweigh the harms, which means that PSA screening is an early-phase clinical trial, and not evidence based. PSA screening with subsequent treatment should be conducted as a clinical trial, not as a routine medical procedure covered by publicly funded health insurance, and the cost should be paid either by the participants themselves or by the research fund (5).

Phase 3 trials of PI-RADS will have to wait until the results of those tremendous labor- and budget-intensive phase 3 and 4 trials regarding PSA screening and MRI are available.

Footnotes

Disclosures of conflicts of interest: T.T. No relevant relationships.

References

  • 1. Yilmaz EC , Shih JH , Belue MJ , et al . Prospective Evaluation of PI-RADS Version 2.1 for Prostate Cancer Detection and Investigation of Multiparametric MRI-derived Markers . Radiology 2023. ; 307 ( 4 ): e221309 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. US Preventive Services Task Force ; Grossman DC , Curry SJ , et al . Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement . JAMA 2018. ; 319 ( 18 ): 1901 – 1913 . [Published correction appears in JAMA 2018;319(23):2443.] [DOI] [PubMed] [Google Scholar]
  • 3. Fenton JJ , Weyrich MS , Durbin S , Liu Y , Bang H , Melnikow J . Prostate-Specific Antigen-Based Screening for Prostate Cancer: A Systematic Evidence Review for the U.S. Preventive Services Task Force . Rockville (MD) : Agency for Healthcare Research and Quality (US) ; May 2018. . Report No.: 17-05229-EF-1. https://pubmed.ncbi.nlm.nih.gov/30085502/. Accessed October 17, 2023. [PubMed] [Google Scholar]
  • 4. Horton RH , Dunlop MG , Houlston RS , et al . Genetic risk scores may compound rather than solve the issue of prostate cancer overdiagnosis . Br J Cancer 2023. ; 128 ( 1 ): 1 – 2 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Takahashi T . Prostate-Specific Antigen Screening Should Not Be Covered by Publicly Funded Health Insurance . JAMA Oncol 2023. . 10.1001/jamaoncol.2023.0254. Published online April 13, 2023. [DOI] [PubMed]
Radiology. 2023 Nov 14;309(2):e231314. doi: 10.1148/radiol.231314

Response

Enis C Yilmaz 1, Mason J Belue 1, Baris Turkbey 1,✉

We read with interest the letter by Dr Takahashi regarding the need for the next-phase trials for PSA screening and MRI. Although we agree with the author regarding the necessity of these mortality investigations, there are a few points we would like to address.

Regarding PSA screening, American Urological Association (1) and U.S. Preventive Services Task Force (2) underline the importance of shared decision-making between the clinician and the patient. Both recommend a personalized approach, considering patient-specific factors such as genetic predisposition due to mutation and family history of prostate cancer when offering PSA testing. In the era of multiparametric MRI (mpMRI), patients with elevated PSA may be referred to imaging before biopsy. mpMRI has been shown to reduce overdiagnosis rates, safely avoiding a biopsy if no suspicious lesions are found on images due to its high negative predictive value.

In the past decade, mpMRI has been used heavily as a tool to help identify lesions that are suspicious for cancer and to guide biopsies. Many large-scale studies have demonstrated the superiority of MRI guidance in sampling prostate cancer compared with the systematic biopsy approach, with better agreement rates with prostatectomy histopathology (3,4). However, the added value of MRI remains mostly dependent on MRI interpretation. PI-RADS was established to standardize image acquisition and assessment and was iterated twice, with PI-RADS v2.1 being the latest. Prospective investigations such as ours (5) are essential to evaluate and improve these scoring systems.

Dr Takahashi concludes that phase 3 trials of PI-RADS should wait until the phase 3 and 4 trials of PSA screening and MRI are available. Although it would be encouraging to see such longitudinal studies, we should consider that these could take years or even decades. Until then, we should work on improving the existing systems such as PI-RADS that already have a role in the diagnostic pathway of prostate cancer in many institutions.

Comprehensive review is critical when offering patients PSA screening and biopsy. While we wait for the studies investigating the impact of PI-RADS categories on mortality, it is imperative to make sure that the patients are treated properly using the best available tools that the current technology offers.

Footnotes

Disclosures of conflicts of interest: E.C.Y. Member of Radiology In Training trainee editorial board. M.J.B. No relevant relationships. B.T. Co-operative research and development agreements with NVIDIA and Philips; royalties from the National Institutes of Health; patents in the field of artificial intelligence.

References

  • 1. Wei JT , Barocas D , Carlsson S , et al . Early Detection of Prostate Cancer: AUA/SUO Guideline Part I: Prostate Cancer Screening . J Urol 2023. . 10.1097/JU.0000000000003492. Published online April 25, 2023. [DOI] [Google Scholar]
  • 2. US Preventive Services Task Force ; Grossman DC , Curry SJ , et al . Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement . JAMA 2018. ; 319 ( 18 ): 1901 – 1913 . [DOI] [PubMed] [Google Scholar]
  • 3. 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 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. 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 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Yilmaz EC , Shih JH , Belue MJ , et al . Prospective Evaluation of PI-RADS Version 2.1 for Prostate Cancer Detection and Investigation of Multiparametric MRI-derived Markers . Radiology 2023. ; 307 ( 4 ): e221309 . [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Radiology are provided here courtesy of Radiological Society of North America

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