“It has been suggested by some investigators that a negative or stable MRI could replace the surveillance biopsy in men on AS.” – Dr. Badar Mian

With apologies to Ralph Waldo Emerson for paraphrasing a famous saying attributed to him: Build a better prostate biopsy and the urological world will beat a path to your door. For many years, the clinical world has looked for ways to solve the problems of a transrectal ultrasound-guided biopsy (TRUS-Bx):

• Ultrasound can’t “see” cancerous tumors so is uses a systematic but blind pattern
• 12-14 or more needles through the rectal wall pose infection risk
• Bleeding and erectile dysfunction are possible side effects
• TRUS-Bx often overdetects insignificant prostate cancer (PCa) but underdetects significant PCa

Did you know that prostate cancer is the only tumor cancer diagnosed by “scattershot” random needle sticks? No woman with suspicion of breast cancer would put up with a dozen or more needles probing her breast in hopes of hitting the tumor.

One area in which TRUS-Bx is particularly troubling is its use during Active Surveillance (AS) for low-risk PCa. The fact that many doctors require repeat surveillance biopsies at scheduled intervals actually deters an unknown number of PCa patients from complying. Men who had a painful initial experience are understandably reluctant to return for another go-round; plus, the risks of infection and side effects increase with each subsequent TRUS-Bx. However, avoiding a surveillance biopsy risks missing cancer progression to a more dangerous grade or stage. If a noninvasive MRI could replace TRUS-Bx, patients might not exactly beat a path to the doctor’s door, but they would at least be more likely to adhere to their monitoring protocol.

One study suggests keep TRUS-Bx

Dr. Badar Mian is a commentator on published urologic literature. In his January, 2020 column, he presented a study out of Memorial Sloan Kettering and New York Presbyterian/Weill Cornell. It involved 207 very low- or low-risk PCa patients who qualified for Active Surveillance (AS) based on their baseline multiparametric MRI (mpMRI) results and a confirmatory biopsy. The purpose of the study was to determine if “an AS regimen based on magnetic resonance imaging (MRI) or clinical stage changes can detect reclassification to grade group (GG) ≥2 disease compared with scheduled systematic biopsies.”^[i] Simply put, can mpMRI pinpoint disease progression and avoid unnecessary AS biopsies?

The study’s surveillance protocol required MRI at 18 months and 3 years, with surveillance biopsy at 3 years that included both MRI-targeted and 14-core systematic approaches.

The 3-year surveillance biopsy results were compared with the participants’ MRI scores at the start of the study, at 18 months, and at 3 years. In 66 (32%) of the participants, biopsies revealed progression to Gleason Group (GG) ≥ 2 disease. However, the performance of the interval MRI scans was inconsistent in terms of how well they correlated with the final biopsy. In analyzing their data, the team calculated that if repeat AS biopsies were done only when triggered by an increased MRI score or clinical stage, 681 biopsies per 1000 men could be avoided but ≥ Grade Group 2 disease would be missed in 169 cases.

Therefore, the authors concluded that missing nearly 1/5 of upgraded tumors is too great a price to pay for relying on MRI. Since they found mpMRI not consistently reliable, they concluded that “prostate biopsy for men on AS should be performed at scheduled intervals, regardless of stable imaging or examination findings.”^[ii] Accordingly, mpMRI should not replace surveillance biopsies at prescribed intervals even if the imaging is stable over time, or does not reveal significant PCa.

Another study finds consistent correlation

On the other hand, a 2020 paper out of Johns Hopkins addresses whether mpMRI during AS improves risk stratification and the detection of hidden upgraded disease.^[iii] In this study, the authors used 432 case records from their AS registry since 2013 (the year they adopted mpMRI as part of AS). All patients had been biopsy-diagnosed as GG 1 and all had undergone a baseline mpMRI scan. Based on their MRIs, the cases were divided into two groups: a) 207 men with one or more PI-RADS ≥3 lesions; and b) 225 men with no PI-RADS ≥3 lesions. These two groups were compared with 669 GG 1 AS patients prior to adoption of mpMRI in 2013 (none of them had baseline imaging). The authors sought to compare upgrade-free survival rates among the three groups to learn if the addition of mpMRI into the surveillance protocol improved detection of hidden progression to a higher-grade group.

At the time of enrollment into AS, the men in the pre-MRI years had an average of 3 surveillance biopsies (range 2-5) at average intervals of 13 months, while men in both mpMRI groups had an average of 2 (range 2-3) surveillance biopsies at average intervals of 12 months. The rate of upgrades to GG ≥2 in all three groups at 2 and 4 years was calculated and compared. The authors found that mpMRI significantly improved the accuracy of risk stratification before and during AS, and correlated well with biopsy, concluding that mpMRI “should be used to aid enrollment and monitoring decisions.”

In fact, a previous Johns Hopkins study of 96 patients, comparing surveillance biopsies with surveillance mpMRI, was more thorough and specific in analyzing the mpMRI scan results than the MSK/NYU/WC study I first described. If a patient’s tumor was “invisible” on three MRI functional sequences (no signal abnormality on T2-weighted images, no focal restricted diffusion, and no perfusion abnormality on dynamic contrast-enhanced images), when correlated with biopsy results the authors found that such imaging results was prognostic for no tumor progression in grade or stage.^[iv] They concluded, “The MR-invisibility of tumor on MP MRI could be of prognostic significance in monitoring men in AS with potential benefit of tailoring the frequency of surveillance biopsies and reducing the number of unnecessary biopsies.”

A work in progress?

Clearly, the idea that mpMRI can and will replace unnecessary repeat biopsies during AS remains debated. All of the institutions cited above are highly respected. I believe that none of the authors wants to hurt patients or put them in harm’s way if it can be avoided. Certainly, those whose caution leads them to the conservative course of prescheduled repeat biopsies during AS do so because they value the patient’s best interest.

While I have confidence in mpMRI scans performed on a powerful 3T magnet, the literature demonstrated that they are not 100% accurate—but neither is systematic biopsy. In radiology and urology, we’re all striving to invent a “better mousetrap” to catch PCa with the greatest accuracy yet the least risk to patients.

This is a work in progress, and we’re getting closer with every passing day. Although a needle biopsy is still the only way to diagnose the grade and genomic factors of actual PCa cells, the day is coming when accurately diagnosed low-risk PCa patients who go on AS can safely be monitored by PSA blood tests and mpMRI scans—and only rebiopsied with in-bore MRI-guided targeted biopsies when imaging shows it’s necessary.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Chesnut GT, Vertosick EA, Benfante N, Sjoberg DD et al. Role of Changes in Magnetic Resonance Imaging or Clinical Stage in Evaluation of Disease Progression for Men with Prostate Cancer on Active Surveillance. Eur Urol. 2019 Dec 21.
[ii] Ibid.
[iii] Mamawala MK, Meyer A, Landis P, Macura KJ et al. Utility of multiparametric MRI in the risk stratification of men with Grade Group 1 prostate cancer on active surveillance. BJU Int. 2020 Feb 10.
[iv] Magnetic resonance-invisible versus magnetic resonance-visible prostate cancer in active surveillance: a preliminary report on disease outcomes. Dianat SS, Carter HB, Peinta KJ et al. Urology. 2015 Jan;85(1):147-53.