Synopsis

Nomograms for prediction of prostate biopsy outcomes incorporating qualitative and quantitative findings of IMPROD biparametric MRI (IMPROD bpMRI consists of T2 weighted imaging and three separate DWI acquisitions) were developed using data of 161 men enrolled as a part of the single-institutional IMPROD (NCT01864135) trial and externally validated in 338 men enrolled as a part of the multi-institutional MULTI-IMPROD(NCT02241122) trial. A nomogram using IMPROD bpMRI findings had area under the curve values (95% confidence interval) of 0.92 (0.88-0.96), and 0.88 (0.84-0.92) in the development and validation cohorts, respectively, for the detection of prostate cancer with Gleason score 3+4 or higher.

INTRODUCTION

METHODS

Between March 2013 and February 2015, 175 men with a clinical suspicion of PCa were enrolled as a part of the IMPROD trial (NCT01864135) while between September 2014 and May 2017, 364 men with the same enrolment criteria were enrolled in the prospective registered validation trial (MULTI-IMPROD, NCT02241122) at four different institutions in Finland (Figure 1). Men with no prior diagnosis of PCa and two repeated PSA measurements ranging from 2.5-20.0 ng/mL and/or abnormal DRE were enrolled.

IMPROD bpMRI was performed using a 3T MR scanner and surface array coils (6,7). IMPROD bpMRI consists of T2-weighted imaging (T2w) and three separate epi read-out based diffusion weighted imaging (DWI) acquisitions (5 b-values 0-500 s/mm2, 2 b-values 0-1500 s/mm2, 2 b-values 0-2000 s/mm2). All imaging data sets were reported by a local radiologist and confirmed or re-reported centrally by one designated central reader to guarantee reporting integrity. The central reader was blind to all clinical data such as PSA, age, patient’s past medical history. Before the initiation of the IMPROD trial, a dedicated IMPROD bpMRI reporting system was developed (IMPROD Likert scoring system, http://petiv.utu.fi/improd). The probability of a suspicious lesion containing Gleason grade 4 was prospectively assigned based on the apparent diffusion coefficient (ADCm) maps calculated using a monoexponential fit and 5 b-values in the range of 0 to 500 s/mm2. This probability was expressed as DWI based Gleason grade score (DbGGS): 1. unlikely- ADCm above or equal to 850 x 10-6 mm2/s, 2. probable: ADCm below 850 x 10-6 mm2/s 3. highly probable- ADC below 750 x 10-6 mm2/s. Men with Likert score 3-5 had two targeted biopsies (TBs) of the dominant lesion followed by 12-core systematic biopsy (SB) while men with a Likert score of 1-2 had only SB. Clinically significant PCa (SPCa) was defined as Gleason score 3+4 or higher.

The primary end point of the combined analysis was the diagnostic accuracy of the combination of IMPROD bpMRI and clinical variables for the detection of SPCa. The “gold standard” for predicting the presence of SPCa was based on TB and SB findings. The following scenarios were explored: 1. Basic model: PSA, age, use of 5-alpha-reductase inhibitors. 2. Visit model: PSA, age, use of 5-alpha-reductase inhibitors, DRE; 3. TRUS model: PSA, age, use of 5-alpha-reductase inhibitors, DRE, TRUS findings, prostate volume (as measured by TRUS), PSA density (dPSA); 4. MRI model: PSA, age, use of 5-alpha-reductase inhibitors, DRE, TRUS findings, prostate volume, dPSA, IMPROD bpMRI Likert score (see http://petiv.utu.fi/improd); 5. MRI model including diffusion weighted imaging (DWI): PSA, age, use of 5-alpha-reductase inhibitors, DRE, TRUS findings, prostate volume (as defined by TRUS), dPSA, bpMRI Likert score, DWI score (DbGGS, details at http://petiv.utu.fi/improd). Multivariate logistic regression models were fitted and performance was evaluated by area under the curve (AUC).

RESULTS

In total, 161 (161/175, 92%) and 338 (338/364, 93%) men completed the IMPROD and MULTI-IMPROD trials (Table 1, Figure 1), respectively.

TRUS model had AUC for SPCa detection (95% confidence interval, 95%CI) of 0.83 (0.77-0.89) and 0.80 (0.75-0.85) in the development and validation cohorts, respectively. The corresponding values for MRI model (Table 2) were 0.93 (0.89-0.97), and 0.89 (0.85-0.93), respectively. Nomograms for all models are shown in Figure 2.

Main limitation is uncertainty in true PCa and SPCa prevalence in the study cohort since men did not undergo prostatectomy.

DISCUSSION / CONCLUSION

A prediction model/nomogram using IMPROD bpMRI findings demonstrated high accuracy for predicting SPCa in men with an elevated PSA. IMPROD bpMRI appears to be a powerful tool for improved prostate cancer risk stratification in men with a clinical suspicion of prostate cancer based on elevated PSA and/or digital rectal examination.

All data are freely are available at the following addresses: http://petiv.utu.fi/improd and http://petiv.utu.fi/multiimprod

Acknowledgements

References

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