Prospective Evaluation of PI-RADS Version 2.1 for Prostate Cancer Detection

Abstract

OBJECTIVE.

The purpose of this study was to prospectively evaluate Prostate Imaging Reporting and Data and System version 2.1 (PI-RADSv2.1), which was released in March 2019 to update version 2.0, for prostate cancer detection with transrectal ultrasound–MRI fusion biopsy and 12-core systematic biopsy.

SUBJECTS AND METHODS.

This prospective study included 110 consecutively registered patients who underwent multiparametric MRI evaluated with PI-RADSv2.1 criteria followed by fusion biopsy and systematic biopsy between April and September 2019. Lesion-based cancer detection rates (CDRs) were calculated for prostate cancer (Gleason grade group, > 0) and clinically significant prostate cancer (Gleason grade group, > 1).

RESULTS.

A total of 171 lesions (median size, 1.1 cm) in 110 patients were detected and evaluated with PI-RADSv2.1. In 16 patients no lesion was detected, and only systematic biopsy was performed. Lesions were categorized as follows: PI-RADS category 1, 1 lesion; PI-RADS category 2, 34 lesions; PI-RADS category 3, 54 lesions; PI-RADS category 4, 52 lesions; and PI-RADS category 5, 30 lesions. Histopathologic analysis revealed prostate cancer in 74 of 171 (43.3%) lesions and clinically significant prostate cancer in 57 of 171 (33.3%) lesions. The CDRs of prostate cancer for PI-RADS 2, 3, 4, and 5 lesions were 20.0%, 24.1%, 51.9%, and 90.0%. The CDRs of clinically significant prostate cancer for PI-RADS 1, 2, 3, 4, and 5 lesions were 0%, 5.7%, 14.8%, 44.2%, and 80.0%. In 16 patients with normal multiparametric MRI findings (PI-RADS 1), the CDRs were 50.0% for PCa and 18.8% for clinically significant prostate cancer.

CONCLUSION.

This investigation yielded CDRs assessed with prospectively assigned PI-RADSv2.1 scores. CDRs increased with higher PI-RADSv2.1 scores. These results can be compared with previously published outcomes derived with PI-RADS version 2.0.

Prostate cancer is the most common solid-organ malignancy and the second leading cause of cancer deaths among American men [1]. For men in whom prostate cancer (PCa) is suspected because of an elevated prostate-specific antigen (PSA) level or abnormal findings at digital rectal examination, the current standard for diagnosis is systematic 12-core biopsy performed transrectally with ultrasound guidance. Because ultrasound has low sensitivity for small tumors within the prostate, this method requires systematic sampling of the whole prostate with needles deployed in a double sextant pattern that is not necessarily aimed at cancer-suspicious areas. This approach can easily result in underdiagnosis of clinically important PCa and delayed therapy [2].

Multiparametric MRI (mpMRI) of the prostate has high sensitivity for cancerous lesions and has been used to identify biopsy targets within the prostate to increase detection of clinically significant cancers [3]. Multiparametric MRI shows the location of suspicious lesions, which can be coregistered in real time with the location on transrectal ultrasound (TRUS) images to target lesions for MRI-TRUS fusion guided biopsy. This method is selective for lesions that are more likely to harbor clinically significant cancer while reducing detection of clinically insignificant cancers [4].

The first standardized prostate MRI guideline was released in 2012 by the European Society of Urogenital Radiology to increase the consistency of radiologic interpretations [5]. Identification of several practical problems identified with this system led to the release of Prostate Imaging Reporting and Data and System version 2.0 (PI-RADSv2.0) in 2015. PI-RADSv2.0 was much simpler than the original system. It gave each lesion a single overall PI-RADS score rather than the summation score proposed in PI-RADSv1.0 [6]. The 2015 version also introduced the idea of dominant sequences to assign an overall PI-RADS score based on lesion location (DWI is dominant in the peripheral zone, and T2-weighted MRI is dominant in the transition zone). Additionally, version 2.0 relegated the dynamic contrast-enhanced (DCE) sequence to a secondary role to be used only to promote PI-RADS category 3 lesions in the peripheral zone to PI-RADS 4 [6].

After PI-RADSv2.0 had been used for several years, a number of objections were raised that prompted reevaluation [7]. PI-RADSv2.1 was released in March 2019 with changes in the definitions of categories 2 and 3 on DW images, categories 1 and 2 on T2-weighted images, and positive versus negative findings on DCE images. These changes of definitions in PI-RADSv2.1 have the potential to affect the scoring of PI-RADS category 2 and 3 lesions and to result in upgrading of category 4 lesions—a concept that was introduced in PI-RADSv2.0 and is defined as lesions with a primary category of 3 on DW images but with positive DCE-MRI findings in the peripheral zone or a category of 3 on T2-weighted images in the transition zone and category 5 on DW images. The changes in definitions and wording are intended to help clarify the subtle differences between lesions in these subcategories to help radiologists make more accurate and reproducible interpretations. Additionally, in the transition zone, a DWI score of 4 or 5 now elevates the overall PI-RADS assessment from category 2–3 for lesions receiving a T2-weighted MRI score of 2 [7].

We conducted a prospective evaluation of the cancer detection rate (CDR), equivalent to the positive predictive value, for each PI-RADSv2.1 category in patients who underwent mpMRI followed by prostate biopsy.

Subjects and Methods

Study Population and Design

This prospective single-institution study received institutional review board approval and was compliant with HIPAA. From April to September 2019, 126 consecutively registered treatment-naïve patients underwent mpMRI with a prospective PI-RADSv2.1 reading and subsequent biopsy. Each patient provided written informed consent. The inclusion criterion for this study was to undergo mpMRI of the prostate followed by systematic 12-core biopsy and MRI-TRUS fusion biopsy. Patients with normal mpMRI findings (PI-RADS category 1) underwent systematic biopsy only if there was no target for fusion biopsy. The exclusion criterion was prior treatment of prostate cancer, including radiation, focal laser ablation, brachytherapy, or androgen deprivation therapy. A total of 126 patients underwent mpMRI with PI-RADSv2.1 scoring and were referred for biopsy. Twelve patients were excluded because they had previously undergone treatment, and four patients were excluded because they did not undergo the biopsy procedure. A total of 110 patients were included in the final study population.

Multiparametric MRI Acquisition and Interpretation

Each patient underwent an mpMRI examination of the prostate with a 3-T MRI system (Ingenia Elition, Philips Healthcare). All patients underwent imaging with an integrated external (surface) phased-array coil; 35 also underwent imaging with an endorectal coil. All imaging studies were interpreted by a single expert genitourinary radiologist with 13 years of experience in prostate imaging. The following sequences were used: T2-weighted MRI, DWI with apparent diffusion coefficient mapping with high b values [b = 1500 s/mm² without endorectal coil, b = 2000 s/mm² with endorectal coil), and DCE-MRI (temporal resolution, 5.6 seconds). The standardized reporting format outlined in PI-RADSv2.1 was used to document all reports. Each lesion found at MRI was assigned scores according to the PI-RADSv2.1 criteria for appearance on both T2-weighted and DW images. DCE-MRI findings were interpreted as positive or negative for each lesion according to PI-RADSv2.1 guidelines. Each lesion was assigned an overall PI-RADSv2.1 score (1–5). Negative mpMRI findings were assigned to PI-RADS category 1.

Biopsy Procedure

Patients were selected for biopsy on the basis of mpMRI findings and clinical suspicion of prostate cancer. Those with suspicious lesions identified with mpMRI underwent fusion biopsy (UroNav system, Invivo). Biopsy specimens were obtained with an 18 × 25 cm spring-loaded core (MaxCore, Bard). The UroNav application overlays T2-weighted images onto real-time TRUS images for lesion targeting. Each lesion was sampled in the axial and sagittal planes.

Each patient underwent systematic biopsy in which 12 cores were obtained in a double sextant pattern, sampling the lateral and medial portions of the apex, mid, and base of each hemigland. All fusion biopsy and systematic biopsy procedures were performed by one of two physicians (one urologist, one interventional radiologist), each with over 10 years of experience in systematic and TRUS-MRI fusion-guided prostate biopsy. Biopsy specimens were assigned Gleason scores by an expert genitourinary pathologist with more than 25 years of experience who was blinded to the MRI findings.

To simplify the reporting of Gleason scores, each cancer-positive lesion was assigned a corresponding International Society of Urological Pathology (ISUP) grade group (ISUP 1 is the equivalent of a Gleason score of 3 + 3; ISUP 2, Gleason 3 + 4; ISUP 3, Gleason 4 + 3; ISUP 4, Gleason 4 + 4; ISUP 5, Gleason sum of 9 or 10) [8]. ISUP 2 or greater was defined as clinically significant PCa (csPCa).

Because it is not possible to accurately match positive systematic biopsy cores to specific lesions identified by means of mpMRI, systematic biopsy was not considered for those who underwent fusion biopsy, because fusion biopsy cores are more accurate for prospective PI-RADSv2.1 validation. Systematic biopsy results were considered only for patients with negative mpMRI findings who did not undergo fusion biopsy.

Statistical Analysis

Lesion-level analysis was performed to determine the proportion of positive lesions in each PI-RADSv2.1 category. A subgroup analysis was performed to analyze the CDRs for primary versus upgraded PI-RADS category 4 lesions, because these upgraded PI-RADS category 4 scores are affected by changes in PI-RADSv2.1. The 95% CIs of proportions and differences in proportions were estimated from the 2.5th and 97.5th percentiles of 2000 bootstrap samples by sampling with replacement on the patient level. The significance of the difference between proportions was determined by the Wald test. Kendall tau-b statistics for clustered data were used to assess the correlation between ISUP grade groups and PI-RADSv2.1 categories [9]. Values of p < 0.05 were considered statistically significant.

Results

The final study cohort included 110 patients (median age, 66 years old; median serum PSA level, 5.79 ng/dL) (Table 1). PCa was diagnosed at biopsy in 59 of 110 patients (53.6%) and csPCa in 43 of 110 (39.1%) (Fig. 1). A total of 171 lesions were detected by means of MRI (peripheral zone, 114; transition zone, 55; central zone, 1; large lesion affecting whole gland, 1). The mean number of lesions detected per patient was 1.56 (SD, 1.1; range, 0–5). The lesions per patient were distributed as follows: no lesion, 16 patients; one lesion, 45; two lesions, 29; three lesions, 12; four lesions, 8). The median lesion size was 1.1 cm. On the lesion level, fusion biopsy detected PCa and csPCa in 43.3% (74/171) and 33.3% (57/171) of targeted lesions, respectively. Additionally, 16 patients with lesion-negative mpMRI results (PI-RADS category 1) underwent systematic 12-core biopsy, and eight of them (50.0%) had at least one core positive for cancer. Three of the 16 (18.8%) had at least one core positive for csPCa.

TABLE 1:

Patient Demographics

Characteristic	Value
Age (y)	66 (58.8–71)
Family history of prostate cancer
Present	38 (34.5)
Absent	72 (65.4)
Prior prostate biopsy
Yes	31 (28.2)
No	79 (71.8)
PSA level (ng/dL)	5.79 (4.54–8.78)
Prostate volume (mL)	55.5 (41–94)
PSA density	0.13 (0.08–0.19)
No. of MRI-detected lesions per patient	1.56 ± 1.1

Note—Except for MRI lesions per patient (mean ± SD), values are median with interquartile range in parentheses or number with percentage in parentheses. PSA = prostate-specific antigen.

Fig. 1—

Chart shows that 59 of 110 patients included in study had cancer detected at biopsy, eight of whom had negative multiparametric MRI results. Distribution of highest International Society of Urological Pathology (ISUP) score for each patient who had cancer at biopsy shows that total of 43 patients had clinically significant prostate cancer (ISUP > 1, red). PI-RADSv2.1 = Prostate Imaging Reporting and Data and System version 2.1.

Figure 2 summarizes lesion characterization according to PI-RADSv2.1 category and pathologic ISUP grade group. Pathologic analysis of targeted biopsy specimens revealed ISUP scores ranging from 0 (benign) to 5. Among the lesions targeted for biopsy, biopsies of 97 of 171 (56.7%) revealed benign tissue. Within the lesions that contained cancer, ISUP 2 (Gleason 3 + 4) was the most common pathologic grade (42% [31/74]), followed by ISUP 1 (23%, [17/74]), ISUP 3 (16% [12/74]), ISUP 5 (15% [11/74]), and ISUP 4 (4% [3/74]).

Fig. 2—

Chart shows that 171 lesions were detected in 110 patients. Fusion biopsy revealed that 97 lesions were benign and 74 were cancer. Distribution of International Society of Urological Pathology (ISUP) scores for cancerous lesions shows that total of 57 lesions were clinically significant prostate cancer (ISUP > 1, red). PI-RADSv2.1 = Prostate Imaging Reporting and Data and System version 2.1.

In a lesion-based analysis, Figure 3 and Table 2 show the CDR for each overall PI-RADSv2.1 category validated by fusion biopsy results. Of the 171 lesions, 67% (115/171) were in the peripheral zone, and 32% (56/171) were in the transition zone. The overall CDR increased with each increase in PI-RADS score beginning with PI-RADS category 2 and greater. There was only one PI-RADS category 1 lesion, so it was grouped with PI-RADS category 2 lesions. The highest CDR was seen for PI-RADS category 5 lesions (PCa, 90.0%; csPCa, 80.0%). The difference in CDRs was statistically significant between PI-RADS categories 3 and 4 for both PCa (p = 0.003) and csPCa (p = 0.001) and between categories 4 (p < 0.001) and 5 (p < 0.001).

Fig. 3—

Chart shows lesion-based cancer detection rate (CDR) for all prostate cancers (PCa) and clinically significant PCa (csPCa) for each Prostate Imaging Reporting and Data and System version 2.1 (PI-RADSv2.1) category as validated by fusion biopsy. Differences in CDR were statistically significant for all PCa and csPCa between PI-RADS categories 3 and 4 and PI-RADS categories 4 and 5.

TABLE 2:

Cancer Detection Rate (CDR) for Each Overall PI-RADSv2.1 Category Validated by Fusion Biopsy Result

PI-RADSv2.1 Category	No. of Positive Lesions	CDR (%)a	95% CI (%)	Difference in CDR Between Consecutive PI-RADS Scores (%)b	95% CI Difference (%)	p
All prostate cancers
≤ 2 (n = 35)	7	20.0	8.3–33.3	4.1.	–13.3 to 21.2	0.644
3 (n = 54)	13	24.1	13.7–35.8	27.8	8.9–44.9	0.003
4 (n = 52)	27	51.9	37.5–65.3	38.1	20.0–56.0	< 0.001
5 (n = 30)	27	90.0	77.8–100
Total (n = 171)	74	43.3	35.0–51.1
Clinically significant prostate cancers
≤ 2 (n = 35)	2	5.7	0–15,2	9.1	–3.3 to 22.4	0.173
3 (n = 54)	8	14.8	6.0–25.6	29.4	12.9–46.5	0.001
4 (n = 52)	23	44.2	30.2–58.5	35.8	16.0–56.3	< 0.001
5 (n = 30)	24	80.0	62.5–96.0
Total (n = 171)	57	33.3	24.4–42.1

Note—PI-RADSv2.1 = Prostate Imaging Reporting and Data and System version 2.1.

^aNumber of positive lesions divided by number of lesions multiplied by 100.

^bCDR_{PI-RADS score + 1} – CDR_{PI-RADS score}.

The results of the subgroup analysis for primary and upgraded PI-RADS category 4 lesions are summarized in Table 3. A total of 52 PI-RADS category 4 lesions were biopsied: 28 were primary category 4 lesions, and 24 were upgraded to category 4 from category 3. The CDR for csPCa within primary PI-RADS category 4 lesions was 60.7% (17/28) and for upgraded lesions was 25.0% (6/24). Overall, 26.1% (6/23) of clinically significant cancers detected in PI-RADS category 4 lesions were in the upgraded category.

TABLE 3:

Cancer Detection Rates for All Prostate Cancers and Clinically Significant Prostate Cancers for Primary and Upgraded PI-RADS Category 4 Lesions

PI-RADSv2.1 Category 4 Subgroup	No. of Positive Findings	No. of False-Positive Findings	Cancer Detection Rate (%)
Overall
Upgraded	7	17	29.2
Primary	20	8	71.4
Clinically significant
Upgraded	6	18	25.0
Primary	17	11	60.7

Note—PI-RADSv2.1 = Prostate Imaging Reporting and Data and System version 2.1.

PI-RADSv2.1 also changed the definition of overall PI-RADS category 3 to include transition zone lesions with a T2-weighted MRI score of 2 and a DWI score of 4 or 5. Three lesions fell into this category, two of which were benign and one of which was pathologically confirmed csPCa (Fig. 4).

Fig. 4—

73-year-old man with prostate-specific antigen level of 6.67 ng/mL. Dashed arrows indicate two additional Prostate Imaging Reporting and Data and System (PI-RADS) category 4 lesions visible in peripheral zone.

A, Axial T2-weighted MR image shows mostly encapsulated nodule (solid arrow) in right mid transition zone. Greatest dimension is 1.2 cm, consistent with PI-RADS score of 2 on T2-weighted image.

B and C, Apparent diffusion coefficient map (B) shows lesion (solid arrow) in same location as lesion in A is hypointense, and DW image (b = 2000 s/mm²) (C) shows it is hyperintense, making it PI-RADS assessment category 4.

D, Dynamic contrast-enhanced MR image shows hypervascularity (solid arrow) within same location as lesion in A–C with early enhancement for overall PI-RADS version 2.1 score of 3, prompting biopsy. MRI–transrectal ultrasound fusion biopsy revealed Gleason 3 + 4 prostate cancer in lesion.

Table 4 shows a cross-tabulation of PI-RADSv2.1 categories and ISUP grade groups. The Kendall tau-b rank correlation between PI-RADSv2.1 score and ISUP grade for all prostate lesions was 0.5 (95% CI, 0.37–0.62; p < 0.001).

TABLE 4:

Distribution of ISUP Grade Groups by PI-RADSv2.1 Category as Determined by Fusion Biopsy

Overall PI-RADSv2.1 Category	Benign	ISUP Grade Group					Total
		1	2	3	4	5
≤ 2	28 (80)	5 (14)	1 (3)	1 (3)	0	0	35
3	41 (76)	5 (9)	7 (13)	0	0	1 (2)	54
4	25 (48)	4 (8)	13 (25)	6 (12)	0	4 (8)	52
5	3 (10)	3 (10)	10 (33)	5 (17)	3 (10)	6 (20)	30
Total	97 (57)	17 (10)	31 (18)	12 (7)	3 (2)	11 (6)	171

Note—Values in parentheses are percentages. ISUP = International Society of Urological Pathology, PI-RADSv2.1 = Prostate Imaging Reporting and Data and System version 2.1.

In this study cohort, 16 patients with PI-RADS category 1 lesions underwent mpMRI (i.e., negative mpMRI results). These patients underwent systematic biopsy because of elevated PSA levels and clinical suspicion of PCa. Eight of the 16 (50%) patients with negative mpMRI results had PCa (ISUP > 0) in at least one core. Within the cohort of eight patients with negative mpMRI and positive systematic biopsy results, the number of positive biopsy cores ranged from 1 to 5 of 12. Furthermore, 3 of 16 patients (19%) had csPCa in at least one core detected with systematic biopsy (ISUP > 1 in 1, 3, and 5 of 12 cores in the three patients).

Discussion

The results of this study show an increase in CDR with increasing PI-RADSv2.1 category with a Kendall tau-b rank correlation of 0.5 between PI-RADSv2.1 categories and ISUP grade groups. Significant differences in CDRs were found between PI-RADS categories 3 and 4 and between categories 4 and 5.

Multiparametric MRI plays an increasing role in the diagnosis of prostate cancer. Performing mpMRI of the prostate before biopsy to detect target lesions helps to reduce the detection of clinically insignificant cancers and increase the diagnosis of clinically relevant cancers [4, 10, 11]. The success of using mpMRI to detect suspicious lesions depends on high-quality image acquisition, interpretation, and reporting. The PI-RADS grading system was developed to standardize the nomenclature and reporting of prostate lesions detected with mpMRI. Originally released in 2012, PI-RADS has been a living document with updated versions released as certain limitations are revealed as experience is gained. PI-RADSv2.1 is the latest iteration.

In 2017, the U.S. National Cancer Institute [13] conducted a prospective study evaluating CDR for PI-RADSv2.0 in a patient population of comparable age and PSA to the patients in the current study: mean age, 64.1 (SD, 7) years old compared with 64.9 (SD, 8) years old in the current study; median PSA level, 6.47 ng/mL (interquartile range [IQR], 4.59–9.31 ng/mL compared with 5.79 ng/mL [IQR, 4.54–8.78 ng/mL] in the current study; median PSA density, 0.11 [IQR, 0.08–0.17] compared with 0.13 [IQR, 0.08–0.19] in the current study). Although the study also revealed an increase in CDR with increasing PI-RADSv2.0 category, the performance of PI-RADSv2.0 was still somewhat disappointing with a Kendall tau-b rank correlation of 0.23 between PI-RADSv2.0 categories and ISUP grade groups. The CDR was lower than expected, particularly within PI-RADS 4 lesions (22.1% for csPCa). Although the CDR for PI-RADS category 4 lesions was much improved in the current study of PI-RADSv2.1 (44% for csPCa), it is still lower than desirable considering PI-RADS 4 is defined as clinically significant cancer is likely to be present.

Although the difference in CDR between the National Cancer Institute study [12] and the current one could be attributable to differences in the pretest probability in each cohort, changes in the updated PI-RADSv2.1 could explain this improvement in CDR for PI-RADS 4 lesions. The definitions of DWI scores of 2 and 3 were revised to be more specific, and the definitions of positive and negative DCE-MRI scores were changed to provide more descriptive detail. Both of these changes affect upgraded PI-RADS category 4 in the peripheral zone, which is defined as a score of 3 on DW images and abnormal DCE-MRI findings. These updates leave less room for subjective interpretations by radiologists and further characterize the lesions that result in fewer “promotions” of category 3 and 4 lesions. For example, the definition of negative DCE-MRI results was updated to include “contemporaneous enhancement” and “focal enhancement corresponding to...extruded BPH [benign prostatic hypertrophy] in the PZ [peripheral zone]” [13], potentially grouping more lesions into the DCE-MRI–negative classification and thus overall PI-RADS 3 instead of 4. This led to improvements in the CDR of category 4 lesions. The CDR for csPCa in upgraded category 4 lesions was higher in our study than it was in the 2017 study evaluating version 2.0 (25% vs 16.2%) [13]. The updated definitions of DWI scores 2 and 3 also resulted in downgrades of many lesions from DWI 3 to DWI 2, including linear and wedge-shaped lesions.

Another change that debuted with the new PI-RADSv2.1 classification was the definition of overall PI-RADS category 3 transition zone lesions to include lesions that have a DWI score of 4 or 5 and a T2-weighted MRI score of 2, which resulted in a PI-RADS score of 2 in version 2.0. This change in definition upgraded three lesions in our study from overall PI-RADS 2 to PI-RADS 3. Because PI-RADS 3 or greater is commonly used as a qualifier for biopsy, this change in definition to overall PI-RADS category 3 has the potential to result in referral of slightly more patients for biopsy. Two of the three lesions in this category were negative for cancer at biopsy, and one lesion was positive for csPCa. Although this sample is not large enough for conclusions about the sensitivity of this newly defined upgraded PI-RADS 3 category, use of version 2.1 led to detection of one additional cancerous lesion and minimally affected scores and biopsy results.

One-half of all patients with completely negative mpMRI findings were found to have cancer at systematic biopsy. Furthermore, 3 of 16 of these patients were found to have clinically significant cancer in at least one core. This forces the question of how sensitive mpMRI is for detecting clinically significant cancers. Artificial intelligence (AI) in medical imaging is rapidly progressing. Several research groups have made developments in prostate cancer AI. A follow-up study could be conducted to test the latest prostate cancer AI models on these normal mpMR images to determine whether AI can be used to detect areas of suspicion on these images that may not be visible to a radiologist.

Limitations

There were a few limitations to this study. First, only one expert radiologist interpreted all mpMR images, which does not reveal information about the interreader reproducibility of the PI-RADSv2.1 grading system. However, a multireader approach is not possible in a prospective study because decisions to biopsy are made by one interpreting radiologist. This is a natural result of conducting a prospective study, and interreader reproducibility should be explored in follow-up studies, because one of the major complaints about PI-RADSv2.0 was variability among readers [14].

Another limitation was that the reference standard for detecting cancer in the prostate was based on biopsy and not whole-mount prostatectomy specimens. However, using whole-mount prostate specimens as validation would select for patients at higher risk because only patients who met prostatectomy criteria would have been included. The results might not be generalizable to the population of patients routinely undergoing MRI, many of whom, if they have cancer, are monitored with active surveillance or undergo radiation therapy.

Conclusion

PI-RADSv2.1 appears to be an improvement over PI-RADSv2.0. CDR increases within each PI-RADSv2.1 category with statistically significant differences in CDR for PI-RADSv2.1 categories of 3 or greater. Compared with previous iterations of PI-RADS, PI-RADSv2.1 includes changes that could improve the CDR of overall PI-RADS category 4. Although PI-RADS scoring is generally a reliable tool for detecting prostate cancer, some clinically significant cancers can still be missed.