1. PROSTATE CANCER CIRCULATING BIOMARKER CONSENSUS STATEMENT QUESTIONS

2. In your opinion, is cell-free DNA testing ready for use in daily routine clinical practice?
Yes
No but current data supports testing in prospective trials
No and further clinical studies are required prior to prospective, clinical validation studies
Abstain/Unqualified to answer
Detailed voting results
Option 1 1
Option 2 10
Option 3 6
Option 4 N 17

3. Detailed voting results
In your opinion, is quantitative analysis of cell-free DNA concentration ready for use in daily routine clinical practice?
Yes
No but current data supports testing in prospective trials
No and further clinical studies are required prior to prospective, clinical validation studies
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 7
Option 3 11
Option 4 N 18

4. In your opinion, is tissue based germline and/or somatic analysis of gene panels ready for use in daily routine clinical practice?
Yes
No but current data supports testing in prospective trials.
No and further clinical studies are required prior to prospective, clinical validation studies.
Abstain/Unqualified to answer
Detailed voting results
Option 1 7
Option 2
Option 3 2
Option 4 1 N 17

5. Based on current knowledge what is the most appropriate clinical situation for cell-free circulating DNA testing if the tests were readily available?
Before starting treatment for metastatic prostate cancer
Before starting first-line mCRPC treatment
Before starting ≥second line mCRPC treatment
All of the above
No appropriate clinical situation currently
Abstain/Unqualified to answer
Detailed voting results
Option 1 1
Option 2
Option 3 6
Option 4 5
Option 5 3
Option 6 N 17

6. Based on the current knowledge what is the most appropriate clinical situation for CTC testing if the tests were readily available?
Before starting treatment for metastatic prostate cancer
Before starting first-line mCRPC treatment
Before starting ≥second line mCRPC treatment
All of the above
No appropriate clinical situation currently
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 5
Option 3 3
Option 4 7
Option 5
Option 6 N 18

7. In your opinion, is genomic analyses of cell-free, gene panel DNA testing ready for use in daily routine clinical practice?
Yes
No but current data supports testing in prospective trials.
No and further clinical studies are required prior to prospective, clinical validation studies.
Abstain/Unqualified to answer
Detailed voting results
Option 1 1
Option 2 13
Option 3 4
Option 4 N 18

8. In your opinion, is CTC testing ready for use in daily routine clinical practice?
Yes
No but current data supports testing in prospective trials.
No and further clinical studies are required prior to prospective, clinical validation studies.
Abstain/Unqualified to answer
Detailed voting results
Option 1 6
Option 2 11
Option 3 1
Option 4 N 18

9. In your opinion, is CellSearchTM CTC count estimation ready for use in daily routine clinical practice?
Yes
No but current data supports testing in prospective trials.
No and further clinical studies are required prior to prospective, clinical validation studies.
Abstain/Unqualified to answer
Detailed voting results
Option 1 12
Option 2 4
Option 3 2
Option 4 N 18

10. In your opinion, is genomic analysis of CTCs ready for use in daily routine clinical practice?
Yes
No but current data supports testing in prospective trials.
No and further clinical studies are required prior to prospective, clinical validation studies.
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 11
Option 3 7
Option 4 N 18

11. In your opinion, is AR-V7 testing ready for use in daily routine clinical practice?
Yes
No but current data supports testing in prospective trials.
No and further clinical studies are required prior to prospective, clinical validation studies.
Abstain/Unqualified to answer
Detailed voting results
Option 1 1
Option 2 13
Option 3 4
Option 4 N 18

12. Which AR-V7 test should be employed in daily routine clinical practice if only one test was funded?
EPIC AR V7 CTC protein assay
Hopkins/Qiagen AR-V7 RT-PCR CTC assay
Custom RT-PCR based CTC assay
Custom protein-based CTC assay
Any/either of these tests
No appropriate assay currently
Abstain/Unqualified to answer
Detailed voting results
Option 1 4
Option 2 1
Option 3
Option 4
Option 5
Option 6 6
Option 7 N 17

13. In your opinion, is AR copy gain/mutation in cell-free DNA testing ready for use in daily routine clinical practice?
Yes
No but current data supports testing in prospective trials.
No and further clinical studies are required prior to prospective, clinical validation studies.
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 15
Option 3 3
Option 4 N 18

14. Based on the current knowledge what is the most appropriate clinical situation for AR- V7/AR copy gain/AR mutation testing if the test were readily available?
Before starting treatment for metastatic prostate cancer
Before starting first-line mCRPC treatment
Before starting ≥second line mCRPC treatment
All of the above
No appropriate clinical situation currently
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 3
Option 3 5
Option 4
Option 5 4
Option 6 1 N 18

15. In your opinion, are cfDNA assays likely to impact patient care by 2020?
Yes
Likely
Possibly No
Abstain/Unqualified to answer
Detailed voting results
Option 1 12
Option 2 3
Option 3 2
Option 4 1
Option 5 N 18

16. In your opinion, are CTC assays likely to impact patient care by 2020?
Yes
Likely
Possibly No
Abstain/Unqualified to answer
Detailed voting results
Option 1 6
Option 2
Option 3 5
Option 4 1
Option 5 N 18

17. In your opinion and if you had a choice is a biopsy assay preferable to a blood-based assay when both are feasible?
Yes No
Abstain/Unqualified to answer
Detailed voting results
Option 1 5
Option 2 12
Option 3 1 N 18

18. 17.In your opinion what is the clinical need for: Circulating biomarkers for DIAGNOSTIC purposes
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 8
Option 2 5
Option 3
Option 4 N 18

19. 18.For which clinical situation is the development of circulating biomarkers for DIAGNOSTIC use most relevant?
Population-based screening for prostate cancer
Localised/locally-advanced prostate cancer
Recurrence after radical treatment
Metastatic prostate cancer
Abstain/Unqualified to answer
Detailed voting results
Option 1 9
Option 2 2
Option 3 1
Option 4 6
Option 5 N 18

20. In your opinion what is the clinical need for: PROGNOSTIC circulating biomarkers
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 3
Option 2 5
Option 3 10
Option 4 N 18

21. For which clinical situation is the development of PROGNOSTIC circulating biomarkers most relevant?
Population-based screening for prostate cancer
Localised/locally-advanced prostate cancer
Recurrence after radical treatment
Metastatic prostate cancer
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 10
Option 3 3
Option 4 4
Option 5 N 17

22. In your opinion what is the clinical need for: PREDICTIVE circulating biomarkers
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 17
Option 2 1
Option 3
Option 4 N 18

23. For which clinical situation is the development of PREDICTIVE circulating biomarkers most relevant?
Population-based screening for prostate cancer
Localised/locally-advanced prostate cancer
Recurrence after radical treatment
Metastatic prostate cancer
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 2
Option 3
Option 4 16
Option 5 N 18

24. Which systemic therapy is in GREATEST need of a PREDICTIVE circulating biomarker in men with mCRPC?
Abiraterone or enzalutamide
Taxane chemotherapy
Radium-223
PARP inhibition or platinum based chemotherapy
Immunotherapy
All of the above
None of the above
Abstain/unqualified to answer
Detailed voting results
Option 1 2
Option 2
Option 3
Option 4
Option 5 5
Option 6 9
Option 7
Option 8 N 18

25. Which systemic therapy has the LEAST need of a PREDICTIVE circulating biomarker in men with mCRPC?
Abiraterone or enzalutamide
Taxane chemotherapy
Radium-223
PARP inhibition or platinum based chemotherapy
Immunotherapy
All of the above
None of the above
Abstain/unqualified to answer
Detailed voting results
Option 1 1
Option 2 3
Option 3 6
Option 4
Option 5
Option 6
Option 7 7
Option 8 N 17

26. A circulating biomarker of DNA homologous repair deficiency would have the greatest clinical utility in which setting?
At diagnosis of localized disease
At diagnosis of metastatic disease
At diagnosis of mCRPC
mCRPC following progression of abiraterone or enzalutamide
mCRPC following progression on all proven therapies
Detailed voting results
Option 1 1
Option 2 8
Option 3 4
Option 4
Option 5 3 N 17

27. In your opinion what is the clinical need for: Circulating RESPONSE biomarkers
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 13
Option 2 3
Option 3 2
Option 4 N 18

28. For which clinical situation is the development of circulating RESPONSE biomarkers most relevant?
Population-based screening for prostate cancer
Localised/locally-advanced prostate cancer
Recurrence after radical treatment
Metastatic prostate cancer
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2
Option 3
Option 4 17
Option 5 N

29. In your opinion what is the clinical need for: Circulating biomarkers as surrogate endpoints for clinical trials
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 13
Option 2 1
Option 3 4
Option 4 N 18

30. For which clinical situation is the development of circulating biomarkers as surrogate endpoints for clinical trials most relevant?
Population-based screening for prostate cancer
Localised/locally-advanced prostate cancer
Recurrence after radical treatment
Metastatic prostate cancer
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 1
Option 3
Option 4 16
Option 5 N 18

31. Which assay is most important as a biomarker of progression for clinical management in men with mCRPC?
CTC enumeration
AR-V7 detection
PSA rise
Radiographic progression
Clinical progression
All of the above
Abstain/unqualified to answer
Detailed voting results
Option 1 2
Option 2
Option 3 1
Option 4
Option 5 4
Option 6 9
Option 7 N 18

32. If all tests were available, which one would you recommend in the following clinical situations (best performing assay): 31.Men with high-risk localised/locally-advanced prostate cancer
Cell-free DNA quantification
Cell-free DNA quantification and sequencing
CTC enumeration
AR-V7
None
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 5
Option 3 2
Option 4
Option 5 8
Option 6 N 17

33. If all tests were available, which one would you recommend in the following clinical situations (best performing assay): 32.Man with rising PSA after radical local treatment (biochemical recurrence)
Cell-free DNA quantification
Cell-free DNA quantification and sequencing
CTC enumeration
AR-V7
None
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 2
Option 3 1
Option 4
Option 5 14
Option 6 N 18

34. If all tests were available, which one would you recommend in the following clinical situations (best performing assay): 33.Man with newly diagnosed metastatic prostate cancer
Cell-free DNA quantification
Cell-free DNA quantification and sequencing
CTC enumeration
AR-V7
None
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 11
Option 3 2
Option 4
Option 5 4
Option 6 N 17

35. If all tests were available, which one would you recommend in the following clinical situations (best performing assay): 34.Man with metastatic CRPC
Cell-free DNA quantification
Cell-free DNA quantification and sequencing
CTC enumeration
AR-V7
None
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 12
Option 3 4
Option 4 1
Option 5
Option 6 N 18

36. CTC phenotyping and genotyping
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 11
Option 2 5
Option 3 2
Option 4 N 18

37. AR-variant assays
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 6
Option 2 10
Option 3 2
Option 4 N 18

38. Neuroendocrine biomarker analyses
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 4
Option 2 7
Option 3 6
Option 4 1 N 18

39. PTEN loss analyses
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 3
Option 2 4
Option 3 9
Option 4 1 N 17

40. DNA repair defect analyses
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 16
Option 2 1
Option 3
Option 4 N 17

41. RB1 loss Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 2
Option 2 8
Option 3 6
Option 4 1 N 17

42. MMR/MSI signatures
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 12
Option 2 4
Option 3 1
Option 4 N 18

43. Immunological biomarker studies (eg PD-L1, PD-L2)
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 7
Option 2 6
Option 3 5
Option 4 N 18

44. Prostate cancer focused, targeted next generation sequencing gene panel
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1 12
Option 2 6
Option 3
Option 4 N 18

45. Prostate cancer focused, targeted MiR profiling
Very high (high clinical need, development urgently needed)
High (relevant clinical need)
Low (not key priority for this purpose)
Abstain/Unqualified to answer
Detailed voting results
Option 1
Option 2 3
Option 3 13
Option 4 1 N 17

46. HEALTHY VOLUNTEER DATA
Very high importance
High importance
Low importance
Not important
Abstain/Unqualified to answer
Detailed voting results
Option 1 11
Option 2 5
Option 3 1
Option 4
Option 5 N 17

47. REPRODUCIBILITY STUDIES
Very high importance
High importance
Low importance
Not important
Abstain/Unqualified to answer
Detailed voting results
Option 1 17
Option 2
Option 3
Option 4
Option 5 N

48. VARIABILITY STUDIES Very high importance High importance
Low importance
Not important
Abstain/Unqualified to answer
Detailed voting results
Option 1 15
Option 2 1
Option 3
Option 4
Option 5 N 16

49. COMPARISON OF DIFFERENT PLATFORMS
Very high importance
High importance
Low importance
Not important
Abstain/Unqualified to answer
Detailed voting results
Option 1 7
Option 2 5
Option 3 3
Option 4 1
Option 5 N 16

50. QUALIFICATION INVOLVING PROSPECTIVE CLINICAL TRIALS
Very high importance
High importance
Low importance
Not important
Abstain/Unqualified to answer
Detailed voting results
Option 1 14
Option 2 3
Option 3
Option 4
Option 5 N 17

51. HEALTH ECONOMIC ANALYSES
Very high importance
High importance
Low importance
Not important
Abstain/Unqualified to answer
Detailed voting results
Option 1 11
Option 2 5
Option 3 1
Option 4
Option 5 N 17