Diagnostic Performance of Ex Vivo Fluorescence Confocal Microscopy in the Assessment of Diagnostic Biopsies of the Prostate
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Study Design
2.3. Acquisition of FCM-Images and Sample Processing
2.4. Histological Evaluation
2.5. Ex Vivo Fluorescence Confocal Microscopy
2.6. Data Collection and Statistical Analysis
3. Results
3.1. Biopsies Acquired and Diagnoses in Conventional Histology
3.2. Manifestations of Tumor in Available FCM Images
3.3. Representation of Parenchyma in FCM Images
3.4. Diagnosis of Malignancy in FCM Images
3.5. GLEASON Grading in FCM Images
3.6. Pifalls and Clinically Relevant Non-Neoplastic Changes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient | Age | PSA | PIRADS | Indication | Biopsies/Tumor | FCM Images/Tumor | Gleason | ISUP | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
P01 | 65 | 6.5 | 4 | AS | 24 | / | 7 | 12 | / | 6 | 3 + 3 | 1 |
P02 | 68 | 7.8 | 4 | Pre | 35 | / | 0 | 17 | / | 0 | - | - |
P03 | 77 | 3.2 | 3 | AS | 24 | / | 7 | 10 | / | 2 | 4 + 3 | 3 |
P04 | 66 | 16 | 5 | Pre | 30 | / | 0 | 10 | / | 0 | - | - |
P05 | 79 | 11.6 | 5 | Pre | 12 | / | 1 | 12 | / | 1 | 3 + 3 | 1 |
P06 | 60 | 8 | n.o. | AS | 12 | / | 0 | 12 | / | 0 | - | - |
P07 | 57 | 9 | 5 | Pre | 12 | / | 5 | 12 | / | 5 | 3 + 4 | 2 |
P08 | 49 | 1.1 | 5 | Pre | 12 | / | 0 | 12 | / | 0 | - | - |
P09 | 57 | 6.4 | 2 | Pre | 12 | / | 5 | 12 | / | 5 | 4 + 3 | 3 |
P10 | 77 | 7.8 | n.o. | Pre | 12 | / | 0 | 12 | / | 0 | - | - |
P11 | 59 | 9.6 | 4 | Pre | 12 | / | 3 | 12 | / | 3 | 3 + 4 | 2 |
P12 | 79 | 55 | 5 | Pre | 14 | / | 7 | 14 | / | 7 | 5 + 4 | 5 |
P13 | 64 | 11.8 | 3 | Pre | 12 | / | 0 | 6 | / | 0 | - | - |
P14 | 64 | 6.6 | 4 | Pre | 12 | / | 1 | 6 | / | 0 | 3 + 3 | 1 |
P15 | 61 | 3.55 | 3 | Pre | 12 | / | 0 | 9 | / | 0 | - | - |
P16 | 66 | 18.6 | 4 | Pre | 20 | / | 0 | 14 | / | 0 | - | - |
P17 | 78 | 4.68 | 4 | Pre | 21 | / | 1 | 11 | / | 0 | 3 + 3 | 1 |
P18 | 72 | 16.4 | 3 | Pre | 14 | / | 0 | 12 | / | 0 | - | - |
P19 | 74 | 14.55 | 3 | Pre | 14 | / | 0 | 7 | / | 0 | - | - |
P20 | 58 | 5.96 | 5 | AS | 12 | / | 1 | 12 | / | 1 | 3 + 3 | 1 |
P21 | 66 | 5.4 | 3 | Pre | 15 | / | 0 | 14 | / | 0 | - | - |
P22 | 66 | 9.92 | 5 | Pre | 13 | / | 9 | 13 | / | 9 | 3 + 4 | 2 |
P23 | 73 | 8.7 | 5 | Pre | 12 | / | 5 | 12 | / | 5 | 4 + 4 | 4 |
P24 | 69 | 12.9 | 4 | Pre | 12 | / | 5 | 12 | / | 5 | 3 + 3 | 1 |
P25 | 77 | 18 | 5 | Pre | 14 | / | 3 | 14 | / | 3 | 3 + 4 | 2 |
P26 | 61 | 33 | 5 | Pre | 14 | / | 12 | 14 | / | 12 | 3 + 4 | 2 |
P27 | 64 | 32.7 | 5 | Pre | 20 | / | 3 | 20 | / | 3 | 3 + 4 | 2 |
P28 | 52 | 6.39 | 4 | Pre | 16 | / | 6 | 16 | / | 6 | 3 + 3 | 1 |
P29 | 63 | 5.89 | 5 | Pre | 14 | / | 1 | 14 | / | 1 | 3 + 3 | 1 |
P30 | 61 | 3.31 | 5 | Pre | 15 | / | 0 | 15 | / | 0 | - | - |
P31 | 64 | 7.28 | 5 | AS | 12 | / | 1 | 12 | / | 1 | 3 + 3 | 1 |
P32 | 63 | 4.41 | 4 | Pre | 13 | / | 0 | 13 | / | 0 | - | - |
P33 | 69 | 6.86 | 4 | Pre | 15 | / | 0 | 15 | / | 0 | - | - |
P34 | 68 | 7.83 | 4 | AS | 16 | / | 0 | 16 | / | 0 | - | - |
P35 | 55 | 3.81 | 5 | Pre | 15 | / | 0 | 14 | / | 0 | - | - |
total | 544 | / | 83 | 438 | / | 75 |
FCM-Ratings (UT) | FCM-Ratings (BT) | |||||||
---|---|---|---|---|---|---|---|---|
0 | 1 | 2 | 0 | 1 | 2 | |||
FFPE TH/ChB | Benign (n = 363) | 343 | 20 | 0 | 295 | 63 | 5 | |
363 | 358 | |||||||
Carcinoma (n = 75) | 6 | 5 | 64 | 4 | 9 | 62 | ||
11 | 13 | |||||||
Total | 438 | 374 | 64 | 371 | 67 | |||
Sensitivity | 85.3% | 89.3% | ||||||
Specificity | 100% | 98.6% | ||||||
Positive predictive value | 100% | 93.1% | ||||||
Negative predictive value | 97.1% | 96.5% | ||||||
Cohen’s Kappa | 0.90 | 0.85 | ||||||
Level of agreement * | very good | very good |
FCM (UT) | |||||
---|---|---|---|---|---|
0 | 1 | 2 | Σ | ||
FCM (BT) | 0 | 287 | 11 | 1 | 299 |
1 | 58 | 10 | 4 | 72 | |
2 | 4 | 4 | 59 | 67 | |
Σ | 349 | 25 | 64 | 438 | |
Agreement | 287 | 10 | 59 | 356 | |
Kappa | 0.56 | ||||
Level of agreement | moderate |
FCM (UT) | FCM (BT) | ||||
---|---|---|---|---|---|
ISUP Grade 1 | ISUP Grade > 1 | ISUP Grade 1 | ISUP Grade > 1 | ||
FFPE (TH/ChB) | IUSP Grade 1 | 21 | 0 | 18 | 3 |
ISUP Grade > 1 | 16 | 27 | 14 | 27 | |
Biopsies (total) | 64 | 62 | |||
Sensitivity | 63% | 66% | |||
Specificity | 100% | 86% | |||
Positive predictive value | 100% | 90% | |||
Negative predictive value | 57% | 56% | |||
Cohen’s Kappa | 0.52 | 0.46 | |||
Level of agreement | moderate | moderate |
FFPE (TH/ChB) | FCM (UT) | FCM (BT) | |||||||
---|---|---|---|---|---|---|---|---|---|
ISUP | n | False Neg | False ISUP | False Neg | False ISUP | ||||
1 | 31 | 10 | 32% | 0 | 0% | 10 | 32% | 3 | 10% |
2 | 28 | 0 | 0% | 16 | 57% | 2 | 7% | 14 | 50% |
3 | 2 | 0 | 0% | 0 | 0% | 0 | 0% | 0 | 0% |
4 | 9 | 1 | 11% | 0 | 0% | 1 | 11% | 0 | 0% |
5 | 5 | 0 | 0% | 0 | 0% | 0 | 0% | 0 | 0.0% |
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Titze, U.; Hansen, T.; Brochhausen, C.; Titze, B.; Schulz, B.; Gunnemann, A.; Rocco, B.; Sievert, K.-D. Diagnostic Performance of Ex Vivo Fluorescence Confocal Microscopy in the Assessment of Diagnostic Biopsies of the Prostate. Cancers 2021, 13, 5685. https://doi.org/10.3390/cancers13225685
Titze U, Hansen T, Brochhausen C, Titze B, Schulz B, Gunnemann A, Rocco B, Sievert K-D. Diagnostic Performance of Ex Vivo Fluorescence Confocal Microscopy in the Assessment of Diagnostic Biopsies of the Prostate. Cancers. 2021; 13(22):5685. https://doi.org/10.3390/cancers13225685
Chicago/Turabian StyleTitze, Ulf, Torsten Hansen, Christoph Brochhausen, Barbara Titze, Birte Schulz, Alfons Gunnemann, Bernardo Rocco, and Karl-Dietrich Sievert. 2021. "Diagnostic Performance of Ex Vivo Fluorescence Confocal Microscopy in the Assessment of Diagnostic Biopsies of the Prostate" Cancers 13, no. 22: 5685. https://doi.org/10.3390/cancers13225685