Eduardo Thadeu de Oliveira Correia1, Jessie E P Sun2, Mark A Griswold1,2, Sree H Tirumani1, Yilun Sun3, Dan Ma2, Yong Chen2, and Leonardo Kayat Bittencourt1,2
1Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, United States, 2Department of Radiology, Case Western Reserve University, Cleveland, OH, United States, 3Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States
Synopsis
Keywords: Prostate, Prostate, magnetic resonance fingerprinting
Motivation: Prostate MRI alone cannot avoid all unnecessary biopsies in MRI-negative patients. This results in overdiagnosis, added morbidity and overtreatment.
Goal(s): Investigate if MRF-derived T1 and T2 maps alone or in combination with conventional ADC mapping can reduce unnecessary biopsies while maintaining optimal significant prostate cancer detection.
Approach: Regions of interest encompassing the right and left lobes of the peripheral zone were used to compute the mean T1, T2, and ADC values.
Results: With a linear regression of mean T1 and T2 values, 63% of all biopsies could be avoided, at the cost of missing one significant prostate cancer.
Impact: The
use of MR Fingerprinting in prostate biopsy decision-making pathways could reduce
unnecessary biopsies while maintaining optimal detection of significant
prostate cancer in MRI-negative patients with clinically indicated biopsies. The
prospective validation of these findings is crucial for patient outcomes.
INTRODUCTION
Magnetic
resonance imaging (MRI) adhering to the Prostate Imaging Reporting and Data
System (PI-RADS) v2.1 guidelines is internationally adopted for the detection
and characterization of clinically significant prostate cancer (csPCa)1,2. Still, the American Urological
Association3 guidelines recommend not deferring a
prostate biopsy for MRI-negative patients (PI-RADS 1&2) based on MRI
results alone. Clinical risk factors and ancillary tests should be used to select
patients for a systematic biopsy3. Although this reduces the number of
missed csPCa, it also results in overdiagnosis and a considerable number of
unnecessary prostate biopsies performed in patients whose prevalence of csPCa
ranges only from 8-10%. A quantitative MRI technique, MR fingerprinting (MRF), was
shown to improve the characterization of prostatic lesions with exceptional
reproducibility4–7. Therefore, in this retrospective study
of MRI-negative patients who had a clinically indicated biopsy, we aim to investigate if MRF-derived
T1 and T2 maps alone or in combination with conventional ADC mapping can avoid unnecessary
biopsies while maintaining optimal csPCa detection.METHODS
We
retrospectively reviewed our prostate MRF institutional database for patients without
prior history of diagnosis or treatment of prostate cancer, who underwent a
prostate MRF from October 2017 to July 2019, and who had a systematic biopsy up
to 6 months following the MRI. An experienced abdominal radiologist re-scored
the MRIs based on PI-RADS v2.1 guidelines. MRI-negative patients with PI-RADS
1/2 scores were included. Regions of interest (ROIs) encompassing the right and
left lobes of the peripheral zone (PZ) were drawn for three axial slices on ADC
and T2 maps, with T2 ROIs copied to inherently co-registered T1 maps (Figure 1). These ROIs were used to
compute mean T1, T2, and ADC values of the PZ. Logistic regressions were used
to estimate changes in odds of csPCa for increases in mean T1, T2, and ADC
values. Decision curve analysis8 was used to compare
the net benefit of performing systematic biopsies for every patient with a
clinical indication (current clinical standard), with further selecting
patients based on mean T1 or T2 values alone, or in combination with mean ADC
values of the PZ. RESULTS
Eighty-seven
PI-RADS 1/2 patients with negative MRIs and clinically-indicated biopsies were
included. Only 9 of those patients had csPCa on biopsy. Each 100 ms increase in
mean T1 was associated with 46% reduced odds of csPCa (95%CI: 0.34-0.85, p <
0.01), whereas each 20 ms increase in mean T2 was associated with 61% reduced
odds of csPCa (95%CI: 0.16-0.92, p = 0.03). For each 100 mm2/s increase in ADC
values, there was a non-significant 36% reduced odds of csPCa (95%CI:
0.47-1.15, p = 0.18). By setting a mean T1 and T2 threshold for biopsy
selection of <2200 and <100 ms, respectively, 30% of biopsies could be
avoided without missing any csPCa. Moreover, with a linear regression analysis
of mean T1 and T2 values, 63% of biopsies could be optimally avoided, at the
cost of missing one csPCa (Figure 2).
On a decision curve analysis, the combination of mean T1+T2+ADC values and even
mean T1 or T2 values alone outperformed the current clinical standard for
optimal biopsy decisions in the entire threshold probability range (0-25%). For
probability intervals of 0-5%, 5-20%, and 20-25%, respectively, mean T2 alone, a
combination of mean T1+T2+ADC and mean T1 alone, had the highest net benefit
for biopsy selection (Figure 3).DISCUSSION
Our
results show that increases in T1 and T2 values are associated with
significantly lower odds of csPCa. Importantly, T1 and T2 outperformed the
current clinical standard for biopsy selection in the entire probability
threshold range. For instance, using T1 and T2 maps for biopsy selection meant avoiding
63% of all biopsies. The addition of conventional ADC mapping to T1 and T2 maps
also improved the net benefit of MRF for biopsy selection in the majority of
the probability range (5-20%). Based on current data from Medicare9,10, if this approach is validated, we would
avoid up to 180,000 biopsies, 21,600 bleeding or infectious complications, and
5,400 hospitalizations per year. All of which means saving around 360 million
USD. CONCLUSION
Compared
with the current clinical standard, the use of MRF T1 and T2 maps alone or
combined with conventional ADC for biopsy selection significantly reduced the
number of unnecessary prostate biopsies, while maintaining optimal detection of
csPCa in MRI-negative patients with clinically-indicated biopsies. The
prospective validation of these findings is crucial to reduce overdiagnosis as
well as reduce the cost and harm of unnecessary biopsies in patients with
negative prostate MRIs.Acknowledgements
No acknowledgement found.References
1. Barrett
T, Turkbey B, Choyke PL. PI-RADS version 2: What you need to know. Clinical
Radiology. 2015;70(11):1165–76.
2. Barrett T, Rajesh A, Rosenkrantz AB,
Choyke PL, Turkbey B. PI-RADS version 2.1: one small step for prostate MRI.
Clinical Radiology. 2019;74(11):841–52.
3. Wei JT, Barocas D, Carlsson S, Coakley
F, Eggener S, Etzioni R, et al. Early Detection of Prostate Cancer: AUA/SUO
Guideline Part II: Considerations for a Prostate Biopsy. Journal of Urology.
2023;210(1):54–63.
4. Shiradkar R, Panda A, Leo P, Janowczyk
A, Farre X, Janaki N, et al. T1 and T2 MR fingerprinting measurements of
prostate cancer and prostatitis correlate with deep learning–derived estimates
of epithelium, lumen, and stromal composition on corresponding whole mount
histopathology. European Radiology. 2021;31(4):2644.
5. Yu AC, Ponsky LE, Dastmalchian S, Rogers
M, Mcgivney D, Griswold MA. Development of a Combined MR Fingerprinting and
Diffusion Examination for Prostate. Radiology. 2017;283(3):729–38.
6. Panda A, Obmann VC, Lo WC, Margevicius
S, Jiang Y, Schluchter M, et al. MR fingerprinting and ADC mapping for
characterization of lesions in the transition zone of the prostate gland.
Radiology. 2019;292(3):685–94.
7. Panda A, O’connor G, Lo WC, Jiang Y,
Margevicius S, Schluchter M, et al. Targeted Biopsy Validation of Peripheral
Zone Prostate Cancer Characterization With Magnetic Resonance Fingerprinting
and Diffusion Mapping. Investigative Radiology. 2019;54(8):485–93.
8. Vickers AJ, van Calster B, Steyerberg
EW. A simple, step-by-step guide to interpreting decision curve analysis.
Diagnostic and Prognostic Research. 2019 Oct 4;3(1):18.
9. Loeb S, Carter HB, Berndt SI, Ricker W,
Schaeffer EM. Complications after prostate biopsy: data from SEER-Medicare. J
Urol. 2011 Nov;186(5):1830–4.
10. Weiner AB, Manjunath A, Kirsh GM, Scott
JA, Concepcion RD, Verniero J, et al. The Cost of Prostate Biopsies and their
Complications: A Summary of Data on All Medicare Fee-for-Service Patients over
2 Years. Urol Pract. 2020 Mar;7(2):145–51.