Background
Methods
Patient cohort and participating centers
Clinical data management
TMA construction
TMA design
IHC staining and analysis
FISH analysis
Central pathology review
Statistical analyses
Results
Feasibility of the multi-center TMA-based resource
Design and strategy of a biomarker validation process
Interest of the biomarker based on extensive preliminary data | |
Relevance to CPCBN objectives and clinical impact for prostate cancer | |
Cohort size used to determine biomarker status | |
Assay performed on paraffin-embedded tissue or TMA | |
Staining quality and requirements that include the following: • Reliable staining against controls and background levels using an automated stainer • Antibody specificity validated by western blot or IHC/immunofluorescence with appropriate controls • Preferences towards monoclonal antibody use • Preferences towards digital image analysis | |
Specific role in prostate cancer prognosis and supporting statistical data (BCR, development of metastasis, p value) | |
Sufficient resources for biomarker analysis (proposed laboratory, supportive infrastructure, funding, and partners) |
Test and validation TMA evaluation
Sites | |||||
---|---|---|---|---|---|
CHUM | CHUdeQ-UL | MUHC | UHN | VPC | |
EXPECTED BENIGN CORES | 623 | 545 | 627 | 773 | 691 |
Reviewed as Benign | 597 | 436 | 485 | 673 | 511 |
Reviewed as Cancer | 0 | 19 | 67 | 25 | 88 |
Reviewed as Uninformativea | 26 | 90 | 75 | 75 | 92 |
EXPECTED TUMOR CORES | 954 | 1269 | 953 | 1042 | 1135 |
Reviewed as Cancer | 845 | 944 | 707 | 825 | 825 |
Reviewed as Benign | 52 | 133 | 109 | 109 | 192 |
Reviewed as Uninformativea | 57 | 192 | 137 | 108 | 118 |
Sites | Number of Patients | Number of Tumor Cores per Patient | Number of Benign Adjacent Cores per Patient | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
0 | 1 | 2 | 3 | > 4 | 0 | 1 | 2 | 3 | > 4 | ||
CHUM | 304 | 2 | 6 | 55 | 236 | 5 | 1 | 16 | 241 | 37 | 9 |
CHUdeQ-UL | 301 | 1 | 9 | 65 | 98 | 128 | 4 | 130 | 104 | 36 | 27 |
MUHC | 304 | 6 | 26 | 93 | 167 | 12 | 5 | 50 | 208 | 37 | 4 |
UHN | 303 | 9 | 10 | 111 | 119 | 54 | 1 | 37 | 177 | 28 | 60 |
VPC | 300 | 5 | 9 | 58 | 165 | 63 | 5 | 51 | 162 | 49 | 33 |
Total | 1512 | 23 | 60 | 382 | 785 | 262 | 16 | 284 | 892 | 187 | 133 |
Clinical data management
Demographic of the CPCBN cohort
TMA series | Test | Validation | |||
---|---|---|---|---|---|
Number of patients | 250 | 1262 | |||
Mean age at diagnosis | 61 | 61 | |||
Median follow-up (months) | 113 | 120 | |||
N | % | N | % | ||
Gleason score at RP | ≤3 + 3 | 64 | 25.6 | 392 | 31.1 |
3 + 4 | 104 | 41.6 | 499 | 39.5 | |
4 + 3 | 42 | 16.8 | 188 | 14.9 | |
≥4 + 4 | 36 | 14.4 | 175 | 13.9 | |
NA | 4 | 1.6 | 8 | 0.6 | |
pTNM | 2 | 171 | 68.4 | 788 | 62.4 |
3 | 77 | 30.8 | 453 | 35.9 | |
4 | 2 | 0.8 | 21 | 1.7 | |
Margin status | Negative | 156 | 62.4 | 837 | 66.3 |
Positive | 91 | 36.4 | 418 | 33.1 | |
NA | 3 | 1.2 | 7 | 0.6 | |
Biochemical relapse | No | 173 | 69.2 | 828 | 65.6 |
Yes | 77 | 30.8 | 434 | 34.4 | |
Type of biochemical relapse | Rising PSA | 54 | 21.6 | 264 | 20.9 |
Failed RP | 16 | 6.4 | 85 | 6.7 | |
Treatment | 7 | 2.8 | 85 | 6.7 | |
Bone metastasis | No | 239 | 95.6 | 1208 | 95.7 |
Yes | 11 | 4.4 | 54 | 4.3 | |
Castrate resistant | No | 237 | 94.8 | 1201 | 95.2 |
Yes | 13 | 5.2 | 61 | 4.8 | |
Mortality | PC specific | 4 | 1.6 | 36 | 2.9 |
Other cause(s) | 17 | 6.8 | 119 | 9.4 | |
Overall | 21 | 8.4 | 155 | 12.3 |
Endpoint | Clinical parameter | Test-TMA cohort | Validation-TMA cohort | ||||||
---|---|---|---|---|---|---|---|---|---|
P
| Exp(B) | 95.0% CI |
P
| Exp(B) | 95.0% CI | ||||
Lower | Upper | Lower | Upper | ||||||
BCR | Serum PSA level |
< 0.001
|
1.064
|
1.042
|
1.086
|
< 0.001
|
1.031
|
1.026
|
1.036
|
Gleason score at RP (6, 3 + 4, 4 + 3, > 8) |
< 0.001
|
2.035
|
1.631
|
2.54
|
< 0.001
|
1.946
|
1.778
|
2.13
| |
pTNM |
< 0.001
|
4.673
|
3.133
|
6.97
|
< 0.001
|
2.599
|
2.202
|
3.067
| |
Margin status |
< 0.001
|
2.392
|
1.517
|
3.77
|
< 0.001
|
2.362
|
1.955
|
2.852
| |
Bone metastasis | Serum PSA level |
0.051
|
1.047
|
1
|
1.096
|
0.047
|
1.018
|
1
|
1.036
|
Gleason score at RP (6, 3 + 4, 4 + 3, > 8) |
0.001
|
3.159
|
1.6
|
6.237
|
< 0.001
|
3.333
|
2.476
|
4.487
| |
pTNM |
< 0.001
|
8.396
|
3.043
|
23.162
|
< 0.001
|
3.882
|
2.422
|
6.22
| |
Margin status | 0.125 | 2.624 | 0.765 | 9.008 | 0.988 | 0.996 | 0.569 | 1.743 | |
PC specific death | Serum PSA level | – | – | – | – |
0.046
|
1.02
|
1
|
1.039
|
Gleason score at RP (6, 3 + 4, 4 + 3, > 8) |
0.001
|
3.159
|
1.6
|
6.237
|
< 0.001
|
3.333
|
2.476
|
4.487
| |
pTNM | – | – | – | – |
< 0.001
|
3.263
|
1.843
|
5.78
| |
Margin status | – | – | – | – | 0.117 | 1.689 | 0.877 | 0.3252 |