PROSTATE CANCER

Integrating and optimizing MRI in monitoring men on active surveillance

Two recent studies have helped to clarify how imaging can be used to inform active surveillance (AS) programmes in men with prostate cancer.

First, in a study published in BJU International, Schwen et al. investigated the combined use of prostate health index (PHI) and multiparametric MRI (mpMRI) to predict grade reclassification (GR) in men on AS.

Although mpMRI has a strong negative predictive value (NPV) for prostate cancer, its solo use for AS monitoring would lead to 10–12% of GRs being missed. However, previous studies have shown that combined use of mpMRI with serum biomarkers can be beneficial in AS. Thus, the team investigated the utility of PHI — a blood test that combines all three forms of PSA (total PSA, free PSA and p2PSA) into one formula for prostate cancer diagnosis — in combination monitoring of men on AS. “The aim of this study was to find novel ways to add greater confidence to AS decision-making by combining biomarkers with mpMRI with the ultimate goal of reducing prostate biopsy frequency without missing GR events,” Schwen tells Nature Reviews Urology.

Patients who had undergone mpMRI and PHI testing within 6 months of each other were retrospectively identified from the John Hopkins AS programme (n = 253). All men underwent transrectal biopsy at diagnosis and surveillance, and GR — defined by the presence of any Gleason score >6 — was assessed at surveillance biopsy. Of the 253 men, 143 (57%) had NCCN very-low-risk disease and 43% (110/253) had NCCN low-risk disease. At biopsy, 15% (38/253) of men had GR. Of note, 71% of the men had a PI-RADSv2 score ≤3, 70 (28%) of whom had not had regions of interest identified on mpMRI. Patients who experienced GR had a higher median age (70 years versus 68 years; P = 0.009) and higher median PHI values (40.7 versus 32.4; P = 0.001). Using the men’s 25th percentile for PHI had a NPV of 95% for GR.

Univariable analysis showed that men with a PI-RADSv2 >3 had a higher risk of GR than men with PI-RADv2 ≤3 (P < 0.001; AUC 0.67). PI-RADSv2 ≤3 alone had a NPV of 91% for detection of GR, whereas the combination of PI-RADSv2 and 25th percentile PHI increased the NPV to 98%. This combination would enable 20% of surveillance biopsies to be avoided whilst missing only 2.6% of GRs. “Our findings reinforce the concept that biomarkers and mpMRI are additive in terms of prognostic value in the AS population,” summarizes Schwen.

A second study, published in European Urology, reported the 5-year outcomes of a large cohort of men on an imaging-based AS programme. In this report, Stavrinides et al. described the clinical, histological and radiological outcomes of 672 men from an established AS programme at University College Hospital London. Data were collected between 2004 and 2017 and included >3,800 person-years of follow-up.

At 3 years, 84.7% of patients remained on AS, dropping to 71.8% at 5 years. Event-free survival and treatment-free survival were lower in men who had MRI-visible disease or secondary Gleason pattern 4 at baseline. Metastasis developed in 8 men; only 24 men died, and none of these deaths was related to prostate cancer. “The paper gives a thumbnail sketch of how an imaging-based surveillance cohort would evolve if NICE guidance (as of May 2019) is implemented,” comments Stavrinides. “Although it reports outcomes from a single institution with considerable experience in mpMRI, it gives the reader an idea on the rates of mortality, metastasis, upgrading and treatment within the first 5 years.”

Overall, the rates of AS discontinuation, mortality and metastasis in this large MRI-led AS cohort were similar to that of standard (biopsy-led) AS cohorts. However, MRI-led AS would avoid the need for regular biopsy. “Men who consider or even officially enrol on AS do not want to be subjected to multiple, regular sampling and perhaps would be much more compliant with an imaging-based protocol,” explains Stavrinides. “In our experience, men on MRI-based AS are very involved, can be easily followed up and are particularly excited to participate in our AS programme.”

“AS itself can be associated with adverse effects, which could be minimized by optimizing the use of imaging”

AS is beneficial in managing men with low-risk cancer, enabling reassurance without the adverse effects of therapy. However, AS itself can be associated with adverse effects, which could be minimized by optimizing the use of imaging in AS programmes.

References

Original articles

  1. Schwen, Z. R. et al. Prostate health index and multiparametric MRI to predict prostate cancer grade reclassification in active surveillance. BJU Int. https://doi.org/10.1111/bju.15101 (2020)

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  2. Stavrinides, V. Five-year outcomes of magnetic resonance imaging–based active surveillance for prostate cancer: a large cohort study. Eur. Urol. https://doi.org/10.1016/j.eururo.2020.03.035 (2020)

    Article  PubMed  Google Scholar 

Related article

  1. Stabile, A. et al. Multiparametric MRI for prostate cancer diagnosis: current status and future directions. Nat. Rev. Urol. 17, 41–61 (2020)

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Correspondence to Annette Fenner.

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Fenner, A. Integrating and optimizing MRI in monitoring men on active surveillance. Nat Rev Urol 17, 369 (2020). https://doi.org/10.1038/s41585-020-0341-9

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