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MRI-guided active surveillance in prostate cancer: not yet ready for practice

Multiparametric MRI enables early detection of progression and reclassification in patients with low-risk prostate cancer on active surveillance and offers the potential to reduce unnecessary biopsies. However, the reliability and reproducibility of MRI-directed surveillance during follow-up is unclear. A recent study highlights the potential and current shortcomings of this approach.

Refers to Fujihara, A. et al. Multiparametric magnetic resonance imaging facilitates reclassification during active surveillance for prostate cancer. BJU Int. https://doi.org/10.1111/bju.15272 (2020).

For more than one decade, active surveillance (AS) has been the recommended treatment option for low-risk prostate cancer. The primary concern regarding this strategy is the risk of missing clinically significant higher-risk cancer at diagnosis or during the surveillance phase owing to inadequate biopsy sampling. The risk of incorrectly classifying cancer is estimated to vary from 10% to 30%, and the risk of progression during follow-up monitoring can reach 50%1. However, the advent of prostate imaging technologies and the widespread use of imaging-directed biopsy techniques offer the potential to reduce the risk of misclassification at diagnosis without drastically reducing the number of patients eligible for AS2.

Multiparametric MRI (mpMRI) prior to biopsy enables early identification of clinically significant foci undetected by systematic, blinded biopsy, and reassures patients and physicians of the safety of AS when imaging reveals no lesions in the prostate. Thus, pre-biopsy mpMRI and mpMRI-guided biopsy should be considered mandatory procedures before low-risk prostate cancer classification and AS, in addition to PSA level evaluation, clinical examination and systematic biopsy.

The usefulness of prostate MRI as a follow-up tool in AS programmes, as assessed in a recent study from Fujihara et al.3, is not yet established. In their prospective study, Fujihara and colleagues monitored patients with low-risk prostate cancer (grade group 1 only) on AS who had undergone at least one follow-up mpMRI during the surveillance phase to determine the correlation between mpMRI findings and histological progression. The cohort was relatively small (181 men), and the main limitation was that only 19% of patients had undergone a baseline mpMRI before active allocation to an AS programme. In future treatment programmes, 100% of patients should undergo baseline mpMRI, as the rate of subsequent pathological progression was twofold higher in patients without baseline mpMRI than in patients who received mpMRI before inclusion (22% versus 11%; P = 0.07). The lack of baseline MRI data also limited the assessment of radiological progression in the overall cohort as only 68 patients underwent at least two serial mpMRI scans. Despite these shortcomings, this study confirms that PI-RADS score at baseline is strongly correlated with the risk of subsequent radiological and histological progression. PI-RADS score 1–2 (no visible lesion) was associated with pathological progression (upgrade to grade group ≥2) in 12% of patients, whereas PI-RADS score 3–5 was associated with progression in 37% of patients during a follow-up period of 2.2 years. Thus, absence of visible lesions on baseline MRI seems to be an important factor in confidence regarding cancer risk and AS safety.

“mpMRI can detect and guide targeted biopsies to new or progressing lesions … not reached by systematic biopsies”

A further interesting point is the biopsy trigger value of follow-up mpMRI scans. Unfortunately, Fujihara and colleagues did not use the validated PRECISE score4 to determine the likehood of radiological progression. However, in patients who received two or more serial mpMRI scans, the authors demonstrated a significant correlation between MRI progression and biopsy progression (and, therefore, active treatment initiation). In patients with no MRI progression, 2-year biopsy progression-free survival was 95% compared with 85% in patients with MRI progression (P = 0.02). Although this difference appears slight, it will certainly increase with a longer follow-up period. Indeed, a study using the PRECISE tool has demonstrated over a 76-month median follow-up period that 5% of patients who did not show radiological progression (PRECISE score 1–3) experienced clinical progression whereas 61% of patients with radiological progression (PRECISE score 4–5) experienced clinical progression5.

These outcomes highlight the importance of follow-up mpMRI with at least two aims. The first is early identification of cancer progression through guided biopsy: mpMRI can detect and guide targeted biopsies to new or progressing lesions in the anterior zones and extremities of the prostate not reached by systematic biopsies. The randomized ASIST trial6 has shown that MRI before serial biopsy resulted in ~50% fewer AS failures (P = 0.017) and less progression to higher-grade cancer. Second, follow-up MRI enables avoiding unnecessary repeat biopsies: Fujihara et al. demonstrated that if surveillance biopsy was triggered based only on MRI progression, 63% of initially scheduled biopsies would be postponed, although this would miss the histological progression (grade group 2) that occurred in 12% of men with no progression on MRI. Interestingly, no high-grade (grade group ≥3) cancer was missed. This consideration is important as MRI-targeted biopsies can lead to grade inflation by targeting the index lesion7, and small-volume grade group 2 prostate cancer has been shown to be potentially suitable for AS in some settings8. These results offer the opportunity for avoiding or postponing serial biopsies based on stable mpMRI results. However, this study and others often include MRI scans read by expert uro-radiologists, and the generalization of such outcomes to all patients on AS should, therefore, be made with caution. Indeed, reports on AS cohorts have revealed substantial discrepancies between centres in the rates of clinically significant prostate cancer undetected by follow-up MRI, ranging from 15% to 25%9,10. Such results emphasize the need for a uniform standard of MRI assessment to ensure reproducibility between centres.

“unless sufficient MRI diagnostic quality is achieved in daily practice, control biopsies might still be necessary”

Thus, unless sufficient MRI diagnostic quality is achieved in daily practice, control biopsies might still be necessary at regular intervals (at 1 year and every 2 years thereafter) during AS. As highlighted by Fujihara et al.3, MRI can miss cancer progression even when applied by experienced radiologists. Extensive assessment and monitoring of PSA density could help to correct potential imprecise evaluation of progression by MRI and should, therefore, be encouraged. The final objective of refining AS programmes is to reduce unnecessary intervention-related side effects. Before adopting a full MRI-guided AS pathway, the reliability of serial MRI reading must be ascertained. Furthermore, serial MRI must be supplemented by other parameters such as PSA density, and the safety of MRI-based triggers for control biopsy should be confirmed in randomized controlled trials.

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Correspondence to Guillaume Ploussard.

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EAU prostate cancer treatment guidelines: https://uroweb.org/guideline/prostate-cancer/?type=summary-of-changes

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Ploussard, G., Renard-Penna, R. MRI-guided active surveillance in prostate cancer: not yet ready for practice. Nat Rev Urol (2020). https://doi.org/10.1038/s41585-020-00416-2

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