Effects of dynamic contrast enhancement on transition zone prostate cancer in Prostate Imaging Reporting and Data System Version 2.1
Article Category: Research Article
Publié en ligne: 20 janv. 2023
Pages: 42 - 50
Reçu: 09 oct. 2022
Accepté: 18 nov. 2022
DOI: https://doi.org/10.2478/raon-2023-0007
© 2023 Jiahui Zhang, Lili Xu, Gumuyang Zhang, Xiaoxiao Zhang, Xin Bai, Hao Sun, Zhengyu Jin, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Prostate cancer (PCa) is a common malignant tumour and has the second highest incidence of all cancers worldwide in males1; it is the second deadliest among male cancer patients in the United States.2 Prostate-specific antigen (PSA) assays and magnetic resonance imaging (MRI) are widespread in the diagnosis and follow-up examination of PCa, and thus the PCa detection rate continues to increase yearly worldwide.3 MRI is a non-invasive examination and can clearly show the anatomy of the prostate. It is one of the most valuable imaging methods for the diagnosis of PCa.4,5 PCa is primarily located in the peripheral zone, but approximately 25% of PCa cases are located in the transitional zone. The MRI features of PCa in the transitional zone are similar to central glandular benign prostatic hyperplasia (BPH) in signal intensity and morphological characteristics, thus making it difficult to differentiate between BPH and PCa.6 The early diagnosis and timely intervention of PCa is key to improve the prognosis of PCa patients.7 Thus, it is of great significance to improve the diagnostic accuracy of transitional-zone prostate cancer (tzPCa).
The Prostate Imaging Reporting and Data System (PI-RADS) is currently recognized as an important guideline for prostate examination and diagnosis via MRI. The first and second editions of PI-RADS guidelines (v1, v2) were proposed in 2012 and 2015, respectively.8,9 In 2019, PI-RADS Version 2.1 (v2.1) reformulated the research specifications for MRI acquisition technology in prostate scanning and analysed the diagnostic values of multiparametric MRI (mpMRI), which includes T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE)-MRI sequencing.10 A prostate transitional-zone lesion score criterion of PI-RADS v2.1 only includes T2WI and DWI sequences; DCE-MRI has no effect on the transitional-zone lesion score. The benefits and drawbacks of the DCE-MRI sequence for PCa diagnosis are increasingly being recognized. The advantages of omitting the DCE sequence are that it shortens the scan time and reduces examination costs. However, the DCE sequence with a higher spatial resolution could be less prone to motion artefacts, susceptibility arte-facts from metallic implants, or rectal gas. It can be used informally as a “safety-net” or “back-up” sequence to detect lesions that might otherwise be missed on T2WI or DWI,
Prompt intervention is needed for clinically significant prostate cancer (Gleason score ≥ 3 + 4), which usually has poor differentiation, a damaged gland structure, a high degree of malignancy, and strong invasiveness.9 This study used three sequence combinations (T2WI + DWI, T2WI + DCE, and T2WI + DWI + DCE) to analyse the diagnostic value of DCE-MRI for detecting tzPCa and clinically significant transitional-zone prostate cancer (cs-tzPCa) in PI-RADS Version 2.1, using transperineal ultrasound-guided prostate biopsy as the reference standard.
The Institutional Review Board (IRB) of our hospital approved this retrospective study (IRB number JS-2114), and the requirement for informed consent was waived. The clinical and MRI data of 894 patients with prostate diseases admitted to our hospital from January 2015 to December 2019 were continuously collected. The inclusion criteria were as follows: (1) a complete MRI examination including T1WI, T2WI, and DWI with the corresponding apparent diffusion coefficient (ADC) map and DCE sequences; (2) diagnosis confirmed by transperineal ultrasound-guided prostate biopsy after MRI; and (3) no biopsy, radiation therapy, chemotherapy, hormonal therapy, or other therapies prior to MRI examination. The exclusion criteria were as follows: (1) after MRI examination, the lesion was suspected to be located in the peripheral zone (n = 438); (2) poor MRI image quality affected scoring (n = 5); and (3) biopsy or other therapies prior to MRI (n = 26). Figure 1 shows the flowchart of the patient recruitment process. In total, 425 cases were included. Non-tzPCa indicates transitional-zone lesions other than cancer, such as BPH or normal prostate. Free cs-tzPCa indicates transitional-zone lesions other than clinically significant prostate cancer, including insignificant prostate cancer and non-tzPCa.
Figure 1
Flowchart showing the patient recruitment process.
This work used a 3.0-T, eight-channel, surface-phased array coil abdominal MRI scanning system (GE750; GE Health care, Milwaukee, WI, USA). The centre of the coil was placed at the pubic symphysis during positioning and fixed with a band to reduce artefacts from breathing movements. The scan sequence included axial T1WI and T2WI, coronal and sagittal T2WI, DWI, and DCE. When the b-value was 100 and 1000 sec/mm2, we used the corresponding ADC graph for evaluation. Gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) offered enhanced contrast at a dose of 0.1 mmol/kg and a flow rate of 3 ml/s. The MRI image-acquisition parameters are shown in Table 1.
Sequence parameters for prostate MRI
| Parameters | T2WI | DWI | DCE |
|---|---|---|---|
| Sequence | FRFSE | SE-EPI | 3D-GRE |
| TR/TE (ms) | 4137/86 | 4200/90 | 4.3/1.3 |
| Flip angle | 110° | 90° | 12° |
| Echo train length | 32 | 1 | N/A |
| FOV (mm × mm) | 270 × 270 | 360 × 360 | 400 × 400 |
| Matrix size | 288 × 192 | 128 × 96 | 320 × 192 |
| Slice thickness (mm) | 3.0 | 3.0 | 3.0 |
| Other | b values = 0, 50, 100, 150, 200, 500, 800, 1000, 1500, 2000 sec/mm2 | Temporal resolution > 10s, total scan time of 5 min |
DCE = dynamic contrast-enhancement; DWI = diffusion-weighted imaging; FOV = field of view; FRFSE = fast relaxation fast spin echo; SE-EPI = spin echo echo planar imaging; T2WI = T2-weighted imaging; TE = time echo; TR = repetition time; 3D-GRE = 3D-gradient echo
The Gleason grading system for histopathological grading of PCa was adopted.18 Here, cs-tzPCa was confirmed if the tumour’s Gleason score was ≥ 3 + 4 with or without ≥ 0.5-cm3 tumour volume and/or extraprostatic extension.9,19 According to the 2014 International Society of Urological Pathology (ISUP) criteria, cs-tzPCa was defined as ISUP grade≥2.20 Patients biopsied all underwent a 12-core systematic trans-perineal ultrasound-guided prostate biopsy by one urinary specialist. The prostate gland was divided into 11 regions on ultrasound scans. At least one additional targeted biopsy was performed; the cognitive targeted biopsy using cognitive registration was based on zonal anatomy or imaging landmarks such as remarkable nodules. The details of the cognitive targeted biopsy are as follows: first, the urologist reviewed the MRI results; and second, the urologist used the MRI information to perform the targeted biopsy for the most remarkable nodules guided by ultrasound images. A pathologist reported the pathological score of prostate biopsy specimens. The radiologist matched the lesions with the highest PI-RADS v2.1 scores on the MRI images with the pathology report.
Two radiologists with 10 and 5 years of experience in prostate imaging/diagnosis independently analysed the images under double-blinded conditions. The radiologists scored the images of index lesions in each sequence using PI-RADS v2.1 and then calculated scores for T2WI + DWI, T2WI + DCE, and T2WI + DWI + DCE. When multiple lesions were present, the lesion with the highest PI-RADS score was used for statistical analysis. In the case of disagreement between the two radiologists, the final score was discussed with a third radiologist to reach a consensus. On PI-RADS v2.1, both T2WI and DWI scored 1–5 points whereas the DCE score was binary [negative (−) or positive (+)]. The final total score of T2WI + DCE and T2WI + DWI + DCE was increased by one point when the image showed early and focal enhancement (positive) of DCE; the final total score of T2WI + DCE and T2WI + DWI + DCE remained unchanged when the image was negative regarding DCE. The final score was 5 when the image scored 5 on T2WI regardless of the DWI and DCE scores. Detailed scoring criteria are shown in Table 2. Figure 2 shows a case of cs-tzPCa located in the right lobe of the prostate.
Figure 2
Images from a 62-year-old male patient with a total prostate-specific antigen (PSA) of 7.66 ng/mL.
Scoring criteria of transition zone prostate for three sequence combinations
| Scoring Criteria |
||||||
|---|---|---|---|---|---|---|
| T2WI | DWI | DCE | T2WI + DWI | T2WI | + DCE | T2WI + DWI + DCE |
| 1 | 1~5 | − | 1 | 1 | 1 | |
| 1 | 1~5 | + | 1 | 2 | 2 | |
| 2 | 1~3 | − | 2 | 2 | 2 | |
| 2 | 1~3 | + | 2 | 3 | 3 | |
| 2 | 4~5 | − | 3 | 2 | 3 | |
| 2 | 4~5 | + | 3 | 3 | 4 | |
| 3 | 1~4 | − | 3 | 3 | 3 | |
| 3 | 1~4 | + | 3 | 4 | 4 | |
| 3 | 5 | − | 4 | 3 | 4 | |
| 3 | 5 | + | 4 | 4 | 5 | |
| 4 | 1~5 | − | 4 | 4 | 4 | |
| 4 | 1~5 | + | 4 | 5 | 5 | |
| 5 | 1~5 | − | 5 | 5 | 5 | |
| 5 | 1~5 | + | 5 | 5 | 5 | |
DCE = dynamic contrast-enhancement; DWI = diffusion-weighted imaging; T2WI = T2-weighted imaging
SPSS version 22.0 (IBM Corp., Armonk, NY, USA) and MedCalc version 15.0 (MedCalc Software, Ostend, Belgium) were used for statistical analysis. Agreement of readings between the two radiologists was evaluated by a kappa (κ) coefficient with κ > 0.20 indicating no agreement, κ = 0.21–0.40 indicating fair agreement, κ = 0.41–0.60 indicating moderate agreement, κ = 0.61–0.80 indicating good agreement, and κ = 0.81–1.00 indicating excellent agreement. Using PI-RADS ≥ 4 as the positive threshold and prostate biopsy as the reference standard, receiver operating characteristic (ROC) curves for T2WI + DWI, T2WI + DCE, and T2WI + DWI + DCE in the diagnosis of tzPCa and cs-tzPCa were separately drawn to calculate areas under the curve (AUCs), sensitivities, specificities, positive predictive values (PPVs), negative predictive values (PNVs), and accuracies to evaluate the corresponding diagnostic efficacies. We also compared differences among the detection rates of tzPCa and cs-tzPCa via three sequence combinations. The DeLong test was used to evaluate differences among AUCs, and McNemar’s test was used to compare the sensitivities, specificities, and accuracies of different sequence combinations. The chi-square test was used to compare differences among the detection rates.
This study included 425 prostate cases per the aforementioned inclusion criteria. There were 203 cases in the tzPCa group (48%) and 222 in the non-tzPCa group (52%). There were 146 cases in the cs-tzPCa group (34%) and 279 in the free cs-tzPCa group (66%). The patient age range was 34–86 years (mean age, 66 years), and the median PSA value was 9.4 ng/ mL. The main clinical manifestations were elevated PSA, dysuria, frequent urination, and urinary urgency. Abnormalities may be found in the patients during digital rectal examination, including a stiff prostate or palpation of nodules. Table 3 shows the patients’ clinicopathological information.
Clinicopathological data of patients included in this study
| Clinicopathological data | Patients |
|---|---|
| Age (year), Mean ± SD | 66 ± 9.0 |
| T-PSA (ng/ml), Median (Upper and lower quartiles) | 9.4 (6.3 + 15.4) |
| tzPCa, n (%) | 203 (48%) |
| Non-tzPCa, n (%) | 222 (52%) |
| cs-tzPCa, n (%) | 146 (34%) |
| Free cs-tzPCa, n (%) | 279 (66%) |
| Tumor size (mm), Median (Upper and lower quartiles) | 12.7 (9.1 + 22.5) |
| 3 + 3 | 57 (28%) |
| 3 + 4 | 56 (28%) |
| 4 + 3 | 24 (12%) |
| 3 + 5 | 3 (1.5%) |
| 4 + 4 | 18 (8.9%) |
| 4 + 5 | 28 (13.8%) |
| 5 + 3 | 1 (0.5%) |
| 5 + 4 | 13 (6.4%) |
| 5 + 5 | 3 (1.5%) |
cs-tzPCa = clinically significant transitional-zone prostate cancer; PSA = prostate-specific antigen; SD = standard deviation; tzPCa = transitional-zone prostate cancer
The PI-RADS v2.1 scores provided by the two radiologists were analysed for agreement. The reading agreement between PI-RADS v2.1 scores for T2WI + DWI, T2WI + DCE, and T2WI + DWI + DCE was κ = 0.869, 0.855, and 0.868, respectively.
The diagnostic efficacies of three sequence combinations in tzPCa and cs-tzPCa were shown in Tables 4 and 5. The AUCs were 0.863, 0.868, and 0.863 for tzPCa and 0.840, 0.833, and 0.824 for cs-tzPCa in T2WI + DWI, T2WI + DCE, and T2WI + DWI + DCE, respectively. The AUCs of three sequence combinations in diagnosing tzPCa and cs-tzPCa had no significant differences (all
Comparison of diagnostic efficacy of three sequence combinations in tzPCa
| tzPCa (n =203) | Non-tzPCa (n=222) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV(%) | Accuracy (%) | AUC (95% CI) | ||
|---|---|---|---|---|---|---|---|---|---|
| T2WI + DWI | ≥ 4 (n=191) > 4 (n=234) | 161 42 | 30 192 | 79.3 | 86.5 | 84.3 | 82.1 | 83.1 | 0.863 (0.827–0.894) |
| T2WI + DCE | ≥ 4 (n=243) > 4 (n=182) | 172 31 | 71 151 | 84.7 | 68.0 | 70.8 | 83.0 | 76.0 | 0.868 (0.832 + 0.899) |
| T2WI + DWI + DCE | ≥ 4 (n=244) > 4 (n=181) | 174 29 | 70 152 | 85.7 | 68.5 | 71.3 | 84.0 | 76.7 | 0.863 (0.827 + 0.895) |
| a |
0.001 | > 0.001 | NA | NA | 0.002 | 0.424 | |||
| b |
> 0.001 | > 0.001 | NA | NA | > 0.001 | 0.968 | |||
| c |
0.500 | 1.000 | NA | NA | 0.250 | 0.369 |
AUC = area under curve; CI = confidence interval; DCE = dynamic contrast-enhancement; DWI = diffusion-weighted imaging; NPV = negative predictive value; PPV = positive predictive value; tzPCa = transitional-zone prostate cancer; T2WI = T2-weighted imaging
a
Comparison of diagnostic efficacy of three sequence combinations in cs-tzPCa
| cs-tzPCa (n=146) | Free cs-tzPCa (n=279) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | Accuracy (%) | AUC (95%CI) | ||
|---|---|---|---|---|---|---|---|---|---|
| T2WI + DWI | ≥ 4 (n=191) > 4 (n=234) | 121 25 | 70 209 | 82.9 | 74.9 | 63.4 | 89.3 | 77.6 | 0.840 (0.802–0.874) |
| T2WI + DCE | ≥ 4 (n=243) > 4 (n=182) | 129 17 | 114 165 | 88.4 | 59.1 | 53.1 | 90.7 | 69.2 | 0.833 (0.795–0.868) |
| T2WI + DWI + DCE | ≥ 4 (n=244) > 4 (n=181) | 131 15 | 113 166 | 89.7 | 59.5 | 53.7 | 91.7 | 69.9 | 0.824 (0.785–0.869) |
| a |
0.008 | > 0.001 | NA | NA | > 0.001 | 0.430 | |||
| b |
0.002 | > 0.001 | NA | NA | > 0.001 | 0.101 | |||
| c |
0.500 | 1.000 | NA | NA | 0.250 | 0.193 |
AUC = area under curve; CI = confidence interval; DCE = dynamic contrast-enhancement; DWI = diffusion-weighted imaging; NPV = negative predictive value; PPV = positive predictive value; tzPCa = transitional-zone prostate cancer; T2WI = T2-weighted imaging
a
Figures 3 and 4 show the cancer detection rates of three sequence combinations in tzPCa and cs-tzP-Ca. When the PI-RADS score was 4, T2WI + DWI had the highest cancer detection rate. The cancer detection rates of T2WI + DWI were significantly greater than those of T2WI + DCE and T2WI + DWI + DCE in tzPCa (69.4%, 29.8%, and 33.7%, respectively, all
Figure 3
Histograms showing cancer detection rates of tzPCa based on the T2-weighted imaging (T2WI) + diffusion-weighted imaging (DWI), T2WI + dynamic contrast-enhancement (DCE), and T2WI + DWI + DCE.
Figure 4
Histograms showing cancer detection rates of cs-tzPCa based on the T2-weighted imaging (T2WI) + diffusion-weighted imaging (DWI), T2WI + dynamic contrast-enhancement (DCE), and T2WI + DWI + DCE.
Some studies questioned whether DCE is a necessary sequence for routine MRI dynamic scanning of the prostate.13,14,15,16,17 To the best of our knowledge, no prior studies have yet analysed the value of DCE-MRI in diagnosing tzPCa and cs-tzPCa. To investigate whether DCE-MRI can improve the diagnostic accuracy of tzPCa, this study innovatively compared and analysed the diagnostic efficiencies of T2WI + DWI, T2WI + DCE, and T2WI + DWI + DCE for detecting tzPCa and cs-tzPCa. This study had a large sample size and included 425 prostate cases—the results were reliable. The results of this study showed T2WI + DWI had higher specificity and accuracy, and DCE-MRI had higher sensitivity in diagnosing tzPCa and cs-tzPCa. DCE-MRI could have a potential impact on the detection of tzPCa and cs-tzPCa.
The AUCs of three sequence combinations in diagnosing tzPCa and cs-tzPCa had no significant differences. However, AUC values only reflect the global performance of the test; sensitivity and specificity trade-offs must also be compared between the three sequence combinations. The specificity and accuracy of T2WI + DWI was significantly greater than those of T2WI + DCE and T2WI + DWI + DCE in diagnosing tzPCa and cs-tzPCa. The prostate patients with an elevated PSA value and a positive digital rectal examination were more confident in the diagnosis of cancer when DWI results were positive. T2WI + DCE and T2WI + DWI + DCE showed significantly higher sensitivity in both tzPCa and cs-tzPCa. Tamada
Eleven tzPCa cases that were not diagnosed by T2WI + DWI were diagnosed by T2WI + DCE and T2WI + DWI + DCE. The reason is that DCE can clearly show small PCa lesions and improve the sensitivity of diagnosis22, while the T2WI and DWI sequences are more likely to miss small lesions. A previous study demonstrated that DCE also improves the differential diagnosis of lesions located on the front edge of the peripheral zone with an unclear transition zone from the normal transition zone.19 T2WI + DCE and T2WI + DWI + DCE had higher diagnostic sensitivity, which could potentially help reduce repeat biopsies when the results were negative. However, active surveillance is still necessary. PCa is characterized by more angio-genic factors and numerous tumour blood vessels that exhibit increased permeability versus healthy blood vessels. PCa lesions typically enhance earlier and more obviously on DCE than adjacent prostate tissues.23,24 Vascular permeability also increases in benign diseases such as BPH.25 These factors might explain the low specificity and high false-positive rate of T2WI + DCE and T2WI + DWI + DCE in the diagnosis of tzPCa and cs-tzPCa.
When the PI-RADS score was 4, the cancer detection rates of T2WI + DWI were significantly greater than those of T2WI + DCE and T2WI + DWI + DCE in tzPCa and cs-tzPCa, which showed T2WI + DWI had lower false-positive rate than T2WI + DCE and T2WI + DWI + DCE. This may be because when BPH lesions strengthened earlier and were more obvious on DCE than adjacent prostate tissues, and when the score of T2WI or T2WI + DWI was 3, the scores of T2WI + DCE and T2WI + DWI + DCE would be increased by one point, thus becoming 4.
This study does have some limitations: (1) This was a single-centre clinical retrospective analysis, which may have selection bias. In future work, we will use a multi-centre, prospective clinical study. (2) This work used prostate biopsy as the reference standard. Prostate biopsy specimens sometimes did not reflect the final pathological findings, which might have yielded false-negative results. (3) In addition to providing qualitative parameters, DCE-MRI can also provide quantitative and semi-quantitative parameters26, which were not discussed further in this work. It remains unclear whether these parameters are useful in the early diagnosis of tzPCa and cs-tzPCa.
In conclusion, DCE-MRI can improve the sensitivity of diagnosis and has a potential impact on the detection and active surveillance of tzPCa and cs-tzPCa. Meanwhile, DCE-MRI can clearly show small cancers and is useful for small PCa lesion diagnosis.