351 patients were included, of which 54 (15.4%) had a history of 5ARI use, and 297 (84.6%) were 5ARI-naïve. Clinical demographics and serum biomarkers of the two groups are summarised in Table 1. The mean age of the 5ARI group was marginally higher than the non-5ARI group (67.6 vs. 65.6; p = 0.0460).

Prostate-specific characteristics differed between the two groups. Prostate volume (64.9 ± 6.21 vs. 48.1 ± 6.85, p < 0.01), corrected PSA (22.0 ± 16.7 vs. 9.41 ± 8.41; p < 0.01), and corrected PSA density (0.387 ± 0.284 vs. 0.214 ± 0.165; p < 0.01) were significantly higher in the 5ARI group. PHI (35.2 ± 16.2 vs. 47.8 ± 27.1, p < 0.01) and PHI density (0.667 ± 0.460 vs. 1.18 ± 0.847, p < 0.01), however, were significantly lower in the 5ARI group.

Regarding imaging characteristics on MRI (Table 2), there was no significant difference in distribution of index lesions’ PIRADS score between the two groups, χ2(3, N = 351) = 4.06, p = 0.255. There were also no significant differences in the number of lesions between 5ARI users and non-5ARI users, χ2(5, N = 351) = 5.60, p = 0.347. The location of the index lesion was also comparable between the two groups, χ2(2, N = 328) = 0.203, p = 0.904.

The histopathological findings post-biopsy are detailed in Table 3. Overall, rate of detection of prostate cancer was significantly lower in the 5ARI group (46.3%) compared to the non-5ARI group (68.0%), χ2(1, N = 351) = 0.203, p < 0.01. There was also a lower absolute rate of detection of clinically significant prostate cancer in the 5ARI group (31.5% vs. 45.5%), although this difference was statistically insignificant, χ2(1, N = 351) = 3.63, p = 0.0566. The proportion of clinically significant cancers out of all cancers detected was comparable between the two groups (68.0% vs. 66.8%), χ2(1, N = 227) = 0.0137, p = 0.907.

Subgroup analysis was performed on the 5ARI group by duration of 5ARI use, specifically less than 6 months, 6 months to 1 year, and more than 1 year (Table 4). 51/54 patients (94.4%) were included, as duration of 5ARI use was not available for 3 patients.

Between the three groups, there was no significant difference in distribution of index lesions PIRADS score, χ2(6, N = 51) = 5.60, p = 0.468. The subgroup of patients with 5ARI use of longer than 1 year had a higher rate of detection of prostate cancer (63.0%), although this was statistically insignificant, χ2(2, N = 51) = 5.91, p = 0.0521. There was no difference in rate of clinically significant cancers, χ2(2, N = 51) = 3.63, p = 0.0566.

To identify predictive factors for prostate cancer in patients taking 5ARIs, subgroup analysis was also performed for the 5ARI group based on eventual diagnosis post-biopsy (Table 5). There were no significant differences found in corrected PSA (19.6 ± 8.46 vs. 24.1 ± 21.3, p = 0.303) and corrected PSAD (0.456 ± 0.282 vs. 0.329 ± 0.278, p + 0.102) between the cancer and cancer-free groups. However, the group diagnosed with cancer had significantly higher PHI scores (43.5 ± 18.7 vs. 30.0 ± 12.2, p = 0.0403) and PHID (1.03 ± 0.530 vs. 0.437 ± 0.193, p < 0.01).

Similarly, between the group diagnosed with clinically significant cancer and the group with either clinically insignificant cancer or no cancer, there were no significant differences in corrected PSA (20.9 ± 9.33 vs. 22.5 ± 19.2, p = 0.676) and corrected PSAD (0.507 ± 0.319 vs. 0.332 + 0.253, p = 0.0576). However, the group with clinically significant cancer had significantly higher PHI scores (53.2 ± 17.6 vs. 31.8 + 13.7, p = 0.0499) and PHID (1.34 ± 0.468 vs. 0.538 ± 0.334, p = 0.0147) than the group with no clinically significant cancer.

A further subgroup analysis was performed on the 5ARI group with index lesion of PIRADS 3 (Table 6). Between the group found to have cancer and the cancer-free group, there were no significant differences in corrected PSA (17.2 ± 5.90 vs. 30.0 ± 26.7, p = 0.0935), corrected PSAD (0.347 ± 0.168 vs. 0.400 ± 0.366, p = 0.645), PHI (41.8 ± 17.8 vs. 35.0 ± 11.8, p = 0.473), and PHID (0.923 ± 0.532 vs. 0.487 ± 0.218, p = 0.140). Between the groups with and without clinically significant cancer, the corrected PSA (17.3 ± 6.90 vs. 26.3 ± 23.3, p = 0.268) and corrected PSAD (0.364 ± 0.316 vs. 0.383 ± 0.315, p = 0.950) were comparable as well.