Nomogram Incorporating Contrast-Enhanced Ultrasonography Predicting Time to the Development of Castration-Resistant Prostate Cancer

Abstract

Background: It is valuable to predict the time to the development of castration-resistant prostate cancer (CRPC) in patients with advanced prostate cancer (PCa). This study aimed to build and validate a nomogram incorporating the clinicopathologic characteristics and the parameters of contrast-enhanced ultrasonography (CEUS) to predict the time to CRPC after androgen deprivation therapy (ADT).

Methods: Patients with PCa were divided into the training (n = 183) and validation cohorts (n = 37) for nomogram construction and validation. The clinicopathologic characteristics and CEUS parameters were analyzed to determine the independent prognosis factors and serve as the basis of the nomogram to estimate the risk of 1-, 2-, and 3-year progress to CRPC.

Results: T stage, distant metastasis, Gleason score, area under the curve (AUC), prostate-specific antigen (PSA) nadir, and time to PSA nadir were the independent predictors of CRPC (all P < 0.05). Three nomograms were built to predict the time to CRPC. Owing to the inclusion of CEUS parameter, the discrimination of the established nomogram (C-index: 0.825 and 0.797 for training and validation datasets) was improved compared with the traditional prediction model (C-index: 0.825 and 0.797), and when it excluded posttreatment PSA, it still obtained an acceptable discrimination (C-index: 0.825 and 0.797).

Conclusions: The established nomogram including regular prognostic indicators and CEUS obtained an improved accuracy for the prediction of the time to CRPC. It was also applicable for early prediction of CRPC when it excluded posttreatment PSA, which might be helpful for individualized diagnosis and treatment.

Keywords: Castration-resistant prostate cancer; androgen deprivation therapy; contrast-enhanced ultrasonography; nomogram; prostate-specific antigen.

Figure 1.

CEUS-TIC in patients with PCa. The extent of tumor enhancement in (A) is lower than that in (B), suggesting a good prognosis. In (A), the yellow, red, blue, and green ROIs represent the hypo-enhanced tumor in the outer gland, normal outer gland tissue, and normal inner gland tissue, respectively. In (B), the yellow, red, and blue ROIs represent the hyper-enhanced tumor in the outer gland, normal outer gland tissue, and normal inner gland tissue, respectively. CEUS indicates contrast-enhanced ultrasonography; PCa, prostate cancer; ROI, region of interest; TIC, time-intensity curves.

Figure 2.

KM curves for the time to the development of CRPC in the training and validation cohorts. No significant difference in the time to CRPC is observed. CRPC indicates castration-resistant prostate cancer; KM, Kaplan-Meier.

Figure 3.

Spearman correlation between CEUS parameters (PI and AUC) and PCa status (T stage and Gleason score). Correlation between T stage and PI and AUC are plotted in (A) and (B). Correlation between Gleason core and PI and AUC are plotted in (C) and (D). AUC indicates area under the curve; CEUS, contrast-enhanced ultrasonography; PCa, prostate cancer; PI, peak intensity.

Figure 4.

Three nomograms predicting the risk of 1-, 2-, and 3-year progress to CRPC in patients with PCa. Nomogram A: complete nomogram with the 6 independent predictors (A); Nomogram B: nomogram without posttreatment PSA (PSA nadir and time to PSA nadir) (B); Nomogram C: nomogram without CEUS (AUC) (C). ADT indicates androgen deprivation therapy; AUC, area under the curve; CRPC, castration-resistant prostate cancer; PCa, prostate cancer; PSA, prostate-specific antigen.

Figure 5.

ROC curves to evaluate the discriminations of different nomograms. The discriminations are evaluated in the training cohort (A) and in the validation cohort (B). Both indicate that the nomogram A shows the highest discrimination compared with nomogram B and C. Nomogram A: complete nomogram with the 6 independent predictors, Nomogram B: nomogram without posttreatment PSA (PSA nadir and time to PSA nadir), and Nomogram C: nomogram without CEUS (AUC). AUC indicates area under the curve; CEUS, contrast-enhanced ultrasonography; PSA, prostate-specific antigen; ROC, receiver operating characteristic.

Figure 6.

Calibration plots of the 3 nomograms. The calibration plots in the training datasets predicting 1-, 2-, and 3-year valid ADT are shown in (A to C) and those in the validation datasets are shown in (D to F). All plots indicate that the predicted probabilities are almost identical to the actual observations. Nomogram A: complete nomogram with the 6 independent predictors, Nomogram B: nomogram without posttreatment PSA (PSA nadir and time to PSA nadir), and Nomogram C: nomogram without CEUS (AUC). ADT indicates androgen deprivation therapy; AUC, area under the curve; CEUS, contrast-enhanced ultrasonography; PSA, prostate-specific antigen.