In May 2018, the multicenter randomized PRECISION (Prostate Evaluation for Clinically Important Disease: Sampling Using Image Guidance or Not?) trial was published in the New England Journal of Medicine. In this trial, 500 men with elevated PSA and no prior biopsy were randomized to undergo standard TRUS-guided biopsy versus MRI with or without targeted biopsy. In the MRI arm, 28% of participants had a negative MRI (scores less than 3) and did not undergo biopsy. The primary outcome was the proportion of men diagnosed with clinically significant cancer, defined as any Gleason score of 3+4 or higher. Overall, clinically significant cancer was found in 38% of the MRI-targeted biopsy group vs 26% of the standard biopsy group (adjusted difference 12 percentage points, 95% CI 4-20, p=0.005). Although this was a non-inferiority trial, the 95% confidence interval indicated superiority of the MRI-targeted strategy over standard biopsy.
Despite this level 1 evidence, there seems to be a disconnect with insurance coverage for MRI prior to initial prostate biopsy in the United States. The week after publication of the PRECISION trial, I had 2 biopsy-naïve patients whose pre-biopsy MRI was denied by insurance. I personally spoke with the insurance company in both cases, describing the recently published results in the New England Journal of Medicine, to no avail. Understandably, the patients were disappointed since we had discussed the evidence that MRI-targeted biopsy outperforms systematic biopsy and they were not in a position to pay for MRI out of pocket.
I posted the following tweet in March 2018: “Retweet if you agree that insurance should routinely cover pre-biopsy MRI in the United States” with a link to the PRECISION study. There appeared to be widespread support for this sentiment based on 199 retweets (users who re-posted it to their followers), 169 favorites (users who clicked the heart symbol), and more than 44,000 impressions (indicating wide reach of the tweet).
To follow up on this issue 5 months after the PRECISION study was published, I posted 3 new polls on Twitter in August 2018 for US urologists about biopsy-naïve patients:
1. In an ideal world, for what percent of patients would you order an MRI prior to performing a initial prostate biopsy? There were 283 total votes, with the following results: 23% said not routinely, 11% would order for less than 50%, 11% would order for 50%-75%, and 55% would order in more than 75% of patients. The poll also generated discussion among urologists about the utility of MRI in the biopsy-naïve setting.
2. If you order an MRI prior to performing an initial prostate biopsy, how often are you required to do peer-to-peer? A total of 80 people voted, with the following results: 14% never, 16% seldom, 28% sometimes, and 42% often. This poll also generated discussion among urologists about their experience obtaining prior authorization.
While it appears that peer-to-peer discussions are required often or sometimes by the majority of respondents, this was not universal.
3. If you order an MRI prior to performing an initial prostate biopsy, how often is the MRI rejected by insurance? A total of 145 people voted, with the following results: 11% never, 13% seldom, 29% sometimes, and 47% often. Thus, the majority of respondents sometimes or often have MRI rejected by insurance prior to initial biopsy. Frustration was expressed by urologists reporting rejection by insurance despite being aware of the PRECISION results.
Aside from issues with insurance coverage of MRI, other challenges remain in its widespread implementation. For example, studies have shown significant variability in the quality of mpMRI cross centers and in interpretation between radiologists, highlighting the importance of quality control.5 Another challenge is what to do about biopsy in cases where MRI is negative. In PRECISION, a quarter of men had a negative MRI and biopsy was not performed.6 This is controversial, however, since some significant cancers may be missed resulting in potential delayed diagnoses. A recent consensus conference in the UK concluded that pre-biopsy mpMRI scoring should not be the only factor guiding biopsy decisions.5 They suggested that other factors such as age, family history, use of 5-alpha reductase inhibitors, total PSA, PSA kinetics, PSA density, urine dipstick results, prior biopsy results, and patient preference can also be factored into the decision.
Moving forward, an important factor influencing implementation of MRI-based protocols is how to optimally integrate imaging with other markers into the detection and management paradigm. The combination of MRI plus a marker test (such as PSA density or the Prostate Health Index) has higher negative predictive value and therefore greater confidence to exclude a biopsy than MRI alone.7, 8
In conclusion, the improvement of prostate MRI is among the most transformative developments in PCa detection over the past decade. Use of MRI prior to prostate biopsy is rapidly increasing; however, there remain barriers to widespread adoption, with many US urologists reporting persistent difficulty obtaining insurance coverage.
Stacy Loeb, MD, is Assistant Professor of Urology and Population Health, New York University Langone Medical Center, New York.