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Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: a prospective, multicenter study in biopsy-naïve men

  • Rianne J. Hendriks,
  • Marloes M. G. van der Leest,
  • Bas Israël,
  • Gerjon Hannink,
  • Anglita YantiSetiasti,
  • Erik B. Cornel,
  • Christina A. Hulsbergen-van de Kaa,
  • O. Sjoerd Klaver,
  • J. P. Michiel Sedelaar,
  • Wim Van Criekinge,
  • Hans de Jong,
  • Peter F. A. Mulders,
  • E. David Crawford,
  • Jeroen Veltman,
  • Jack A. Schalken,
  • Jelle O. Barentsz,
  • Inge M. van Oort

Publication: Prostate cancer and prostatic diseases, May 2021

Background

Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of “unnecessary” prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy.

Methods

This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥−2.8. Decision curve analysis (DCA) was performed to assess clinical utility.

Results

Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%.

Conclusions

SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

Commentary by Dr. Van den Bergh

A fixed prostate-specific antigen (PSA) threshold as a basis for prostate biopsy is no longer the current standard. In men suspected of prostate cancer (PCa), different tools are now available to risk stratify for biopsy; and reduce unnecessary biopsies,
overdetection of insignificant tumours, and burden for patient and healthcare, while optimising the rates of significant tumours.

In the EAU Guidelines for PCa, the following tools are recommended to use for biopsy indication: risk calculator, imaging, or additional serum, urine or tissue-based test. (1) These tests can be used individually (i.e. only one test is applied), combined
in sequence / conditional (i.e. the first test is performed and only when that outcome is abnormal, a second test is added), or cumulative (i.e. two or more tests both need to be abnormal to indicate biopsy).  

The study by Hendriks et al illustrates how the SelectMDx urinary biomarker test and multi-parametric MRI (mpMRI) perform with regard to biopsy indication and cancer detection rates, and how these could be best combined. (2)

The authors prospectively included patients with a PSA >=3 ng/ml. All received an mpMRI, SelectMDx test and biopsies (systematic, combined with in-bore targeted cores if possible). The different hypothetic pathways using SelectMDx, mpMRI, and combinations
or sequences were studied, using the protocol in which all patients received biopsies as the reference.

The International Society of Urological Pathology (ISUP) grade 2 or higher (Gleason 3+4=7 or higher) was found in 31%. Refraining from biopsy in negative SelectMDx test, biopsy was avoided in 38% and significant tumours were missed in 10%. Using mpMRI
as the only test, 49% of biopsies could be avoided and only 4.9% of significant tumours were missed. A pathway with SelectMDx first, and only when this was abnormal, an additional mpMRI, reduces MRIs in 38%, avoids biopsies in 60% and misses significant
cancer in 13%. All strategies missed many more insignificant than significant cancers. 

Reesink et al previously presented a comparable analysis, but then with the outcomes of different diagnostic pathways possible with the European Randomized study of Screening for Prostate Cancer (ERSPC) prostate risk indicator and biparametric MRI. (3)

In the sequenced strategy, it was found that applying a risk calculator threshold of 20% before MRI, 1 out of 2 MRIs could be avoided while almost 1 out of 5 significant cancers were missed. With a 12.5% threshold, 1 out of 3 MRIs could be avoided and
only 1 out of 10 significant cancers were missed. A strategy with an MRI as the first step in all patients, outperformed any pathway with the risk calculator as the first step. 

The most efficient pathway for patients with suspected PCa is not only decided by biopsy and cancer detection rates. The availability of tests, easiness of use, expertise and experience, and costs may differ per country, region and centre. Furthermore,
pathways may be specified to patient with different age, PSA, and family history characteristics. For patients with very high PSA (e.g. >20 ng/ml) or an abnormal digital rectal examination, other pathways may apply. 

In conclusion, any risk stratification for biopsy over a fixed PSA threshold has dramatically improved the diagnostic pathway, and we now have multiple options available. MRI has the highest diagnostic accuracy, but it is also the most costly. The most
efficient and optimal combination(s) of different available diagnostic tools for each patient and region needs to be further studied. Sequencing tests is an efficient strategy, but it should be remembered that the false negative rates of applied tests
accumulate. 

References: 

Mottet N, van den Bergh RCN, Briers E, 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 Feb;79(2):243-262.  

Hendriks RJ, van der Leest MMG, Israël B, et al. Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: a prospective, multicenter study in biopsy-naïve men. Prostate Cancer Prostatic Dis. 2021 May 3. 

Reesink DJ, Schilham MGM, van der Hoeven EJRJ, et al. Comparison of risk-calculator and MRI and consecutive pathways as upfront stratification for prostate biopsy.World J Urol. 2020 Oct 22.