Reducing Biopsies and MRIs in the Diagnostic Pathway of Prostate Cancer: Application of the Rotterdam Prostate Cancer Risk Calculator to the PRECISION Trial Data

FURTHER VALIDATION OF the Rotterdam Prostate Cancer Risk Calculator (RPCRC) has been demonstrated in a study that applied the RPRCR and RPCRC-MRI to data from patients enrolled in the PRECISION (Prostate Evaluation for Clinically Important Disease: Sampling Using Image Guidance or Not?) trial, which demonstrated that using multiparametric magnetic resonance imaging (mpMRI) for risk assessment prior to performing a prostate biopsy was superior to standard systematic transrectal ultrasound (TRUS)-guided biopsy in biopsy naïve patients at clinical risk for prostate cancer.1

Since the results of the PRECISION trial were published, the big questions surrounding the utilization of MRI have been in clarifying its role in the standard prostate cancer screening work-up and evaluation. Prior to the widespread utilization of mpMRI, men within a specific age range were screened annually with a prostate-specific antigen (PSA) test, a non-specific marker for prostate growth or inflammation. If the PSA was elevated, the patient would undergo a 12-core systematic TRUS- guided prostate biopsy. If the results were positive for local prostate cancer, they would go on with treatment, i.e., surgery, radiation. etc. However, if the prostate biopsy was negative, the patient would continue PSA screening, and if the PSA continued to rise, the patient would potentially undergo multiple prostate biopsies.

With the advent of mpMRI and the associated trials showing its benefit as part of prostate cancer screening workup, a new but simple question emerged: How do we use mpMRI appropriately? Should we indiscriminately obtain a mpMRI on any patient with an elevated PSA prior to prostate biopsy or should it be more selective? If it should be more selective, how do we properly evaluate the patient with an elevated PSA and if they require mpMRI and subsequent prostate biopsy, or neither require mpMRI or prostate biopsy.

The validated Rotterdam Prostate Cancer risk calculator (RCPRC) and RCPRC-MRI (when using mpMRI as part of the algorithm) can be used as an upfront risk calculator in the diagnostic pathway of prostate cancer. The goal is to reduce the number of prostate biopsies and possibly even the number of unnecessary MRIs. The RPCRC is based on the Rotterdam arm of the European Randomized study of Screening for Prostate Cancer (ERSPC) that started in 1993 and is a landmark study for population-based prostate cancer screening.2

Although the RCPRC has been externally validated, concern has remained that there may be a difference between the initial cohort that the RCPRC data was built on and the tested cohort and that calibration and threshold adjustment might need to be made. To identify what intercept adjustment might be necessary to calibrate what was known from a screening cohort (original Rotterdam arm of ERSPC study) and a clinical cohort (RPCRC-MRI), members of the ERSPC Rotterdam study and the PRECISION investigators groups retrospectively evaluated the effect of upfront use of the RPCRC and RPCRC-MRI in prostate biopsy naïve patients with elevated risk based solely on an elevated PSA and normal digital rectal exam (DRE) in the PRECISION trial.

As reported during a moderated poster session by Ivo de Vos, MS, from Erasmus MC, Rotterdam, the potential reduction in systematic biopsies was investigated in 188 men on the TRUS arm of the PRECISION study, the potential reduction in MRIs in 206 men on the MRI arm, and the potential reduction in targeted prostate biopsy in 137 men on the MRI arm who had undergone subsequent MRI-targeted prostate biopsies.

“The performance, including discrimination, calibration, and net benefit of the RPCRC and RPCRC- MRI was good, using data from the PRECISION trial,” Mr. Vos declared. On the TRUS arm, on which all men underwent systemic biopsy, recalibration of the risk stratification calculator was necessary to account for the difference in prevalence (screening vs clinical cohort). To illustrate why recalibration was necessary, Mr. de Vos showed that without recalibration, the median (IQR) probability of men with clinically significant prostate cancer was 9.2 (5.4-20.9), whereas after recalibration it was 29.2 (19.0-51.9). After recalibration, an increased threshold of 20% for any prostate cancer, or 10% for clinically significant prostate cancer, yielded a reduction of 28% of all systemic biopsies and would have missed 5 clinically significant prostate cancer diagnoses (defined as Gleason Grade Group ≥2).

On the MRI arm, only patients with a positive MRI received a targeted biopsy. Had they not received an MRI but undergone only RCPRC risk stratification without recalibration, the number of necessary MRIs would have been reduced by 35%. This finding was consistent with previous studies evaluating the RCPRC-MRI, Mr. de Vos noted. Further, by utilizing the RCPRC-MRI stratification, 9% of all targeted prostate biopsies would be reduced and there would only be one case of a missed cancer diagnosis of one Gleason grade group 2 cancer diagnosis.

Mr. de Vos stressed that the original RCPRC based on a population-based cohort required the PRECISION cohort to calibrate the risk calculator. Further, in addition to calibration, the threshold needed to be adjusted to determine referral to the next step in patients who had not received an MRI. By doing so, nearly 30% of all systematic prostate biopsies could be avoided.

The patients who had an MRI in the PRECISION trial when using the RCPRC-MRI did not require any adjustment at all, and additional value by using the RCPRC on the PRECISION trial patients was limited to reduction of ~10% of prostate biopsies, Mr. de Vos added. By applying the RPCRC, there was potential to reduce the number of MRI’s by more than one-third.

It is critical to evaluate the utilization of MRI in the way that it is adapted in the process of how patients are risk-stratified, Mr. de Vos concluded. The RCPRC is an exciting tool that, with proper calibration and development of an appropriate threshold, can allow for risk stratification of patients with an elevated PSA to determine the need for a) mpMRI and b) prostate biopsy. Furthermore, within the patient population that does receive an MRI prior to undergoing targeted prostate biopsy, the RPCRC-MRI is useful to evaluate which patient may not need to undergo biopsy based on their personal risk assessment. Utilizing the RCPRC and the RCPRC-MRI can also reduce costs associated with mpMRI, as well as reducing patient-related morbidity and improve patient care, Mr. de Vos added.

David Ambinder, MD is a urology resident at New York Medical College / Westchester Medical Center. His interests include surgical education, GU oncology, and advancements in technology in urology. A significant portion of his research has been focused on litigation in urology.

References

  1. Remmers S, Kasivisvanathan V, Moore C, Roobol M, de Vos I. The diagnostic pathway of prostate cancer in the MRI era including risk stratification: applying the Rotterdam prostate cancer risk calculator to the PRECISION trial data. J Urol. 2021;206(3S suppl):e83-e84. DOI: 10.1097/JU.0000000000001972.14
  2. Kasivisvanathan V, Rannikko AS, Borghi M, et al; PRECISION Study Group Collaborators. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018;378(19):1767-1777. DOI: 10.1056/NEJMoa1801993
  3. Schröder FH, Denis LJ, Roobol M, , ERSPC The story of the European Randomized Study of Screening for Prostate Cancer. BJU Int. 2003;92 Suppl 2:1–13