A total of 379 consecutive patients suspected of prostate cancer were referred for prostate biopsy. 32 patients were excluded. Finally, 347 patients were enrolled into the study and evaluated with CETRUS followed by prostate biopsy. No adverse events related to the contrast agent were observed in any of the 347 patients. The mean patient age was 68.5 years (range: 53-79), mean prostate volume was 52.8 mL3 (range: 18-136), and mean PSA was 10.3 ng/mL (range: 1.9-382). Prostate cancer was found in a total of 164 of 347 (47.3%) patients. Among the 164 patients, 91 patients underwent laproscopic radical prostatectomy. 17 patients were excluded. Finally, 74 patients with localized prostate cancer were enrolled and followed up as shown in Figure 1.
The performance of CETRUS in reducing unnecessary biopsy
The proportions of prostate cancer in CETRUS score groups 1-5 were 0% (0/42), 11.5% (6/52), 32.5% (40/123), 87.1% (61/70), and 95.0% (57/60), respectively. A significant positive correlation (r = 0.69, p < 0.001) was found between CETRUS scores and prostate cancer. When cut off at 4 (≤ 3 as BPH and ≥ 4 as prostate cancer), CETRUS score had the highest accuracy of 83.3% (289/347) in the diagnosis of prostate cancer, with a sensitivity and specificity of 90.8% (118/130) and 78.8% (171/217), respectively. ROC analysis showed the AUC of the CETRUS score was 0.89 (95% CI: 0.85-0.92), indicating that CETRUS score can be used to differentiate prostate cancer from benign prostatic hyperplasia (BPH) (Additional Table 1, Fig. 2). Moreover, when cut off at 2 (1 = BPH and ≥ 2 as prostate cancer), CETRUS score had the highest specificity of 100% for differentiating prostate cancer from BPH, indicating that CETRUS with a cut-off score of 2 might be an effective tool for reducing unnecessary prostate biopsy. In this study, performing biopsy when CETRUS score ≥ 2 could have reduced the number of biopsies by 12.1% (42/347) without missing cancer diagnosis and spared 23.0% (42/183) of men from unnecessary biopsy (Table 1).
CETRUS can predict biochemical recurrence after radical prostatectomy in patients with localized prostate cancer
The clinicopathologic characteristics of the 77 patients with localized prostate cancer treated with radical prostatectomy were summarized in Table 2. CETRUS score results were dichotomized into low score (≤ 3) and high score (> 3) groups. No significant correlation was found between CETRUS score and patient age, tumor stage, Gleason score, PSA, BMI, or ECOG PS (p > 0.05, Table 2).
The median age of the 77 patients was 65.1 years (range: 49-74 years), and the median follow-up time was 30 months (range: 8-56 months). Biochemical recurrence was observed in 22% (17/77) of patients during follow-up. The 3-year biochemical recurrence-free survival rates were 86% (95% CI: 73%-93%) for patients with low CETRUS scores and 59% (95% CI: 53%-67%) for patients with high CETRUS scores (Fig. 3). Univariate Cox regression analysis revealed that CETRUS score, clinical stage, Gleason score, PSA level, and ECOG PS had a significant impact on biochemical recurrence-free survival (p = 0.015, 0.042, 0.011, 0.037 and 0.047, respectively, Table 3), while other clinicopathologic variables, including age and BMI, did not (p = 0.618, 0.205, respectively, Table 3). Using multivariate analysis to further examine the parameters that were significant in univariate analysis, we determined that CETRUS score was an independent predictor of biochemical recurrence (HR: 7.02; 95% CI: 2.00-24.69; p = 0.002; Table 3).
To develop a more accurate prognostic tool, we used Cox proportional hazards regression to construct a prognostic model combining CETRUS score and clinicopathologic risk factors. Time-dependent ROC curve was used to compare the predictive accuracy of the combined model with models of CETRUS score alone or individual clinicopathologic factors alone. As shown in Figure 4, the model combining CETRUS score, Gleason score, tumor stage, and PSA (AUC at 3 years: 0.886; 95% CI: 0.754-1.000) had a better prognostic value than the model of CETRUS score alone (AUC at 3 years: 0.696; 95% CI: 0.520-0.890; p=0.006), Gleason score alone (AUC at 3 years: 0.679; 95% CI: 0.554-0.811; p=0.018), tumor stage alone (AUC at 3 years: 0.620; 95% CI: 0.500-0.748; p<0.001), or PSA alone (AUC at 3 years: 0.611; 95% CI: 0.500-0.792; p=0.004). Therefore, CETRUS score may add prognostic value to clinicopathologic risk factors of localized prostate cancer.