This document discusses using biomarkers and gene profiling versus imaging for staging prostate cancer. It notes limitations of imaging including detection limits and inability to distinguish cancer from normal tissue. Biomarkers can help with predicting risk, confirming staging, and early warning before metastasis. Current biomarkers help with clinical staging and recurrence prediction after treatment. Novel techniques like liquid biopsies of circulating tumor cells and cell-free DNA can provide molecular characteristics of tumors and help identify heterogeneity. Combining imaging with molecular markers may allow complementing analyses and identifying new imaging targets from molecular profiles. The next steps involve using liquid biopsies and imaging together to determine metastasis presence, location and characteristics as well as better stratifying patients and finding novel targets.

1. Staging of prostate cancer:
Imaging
vs
Biomarkers and gene profiling
Prof. Dr. Guido Jenster
Experimental Urological Oncology
Erasmus MC, Rotterdam
g.jenster@erasmusmc.nl

2. Biomarkers vs Imaging
Limitations of imaging
- Detection limits: minimal local invasion and micro-metastases
- PCa-specificity: distinguish normal prostate from PCa
- False negative: target-negative (PSMA)
- False positive: abnormalities not related to PCa
Beyond technical issues
- heterogeneity within and between tumors
- molecular characteristics of the tumor
Confirming Predicting
Stratification
Early warning
before event
Costly
Patient burden

3. Biomarkers: Current Status
Primary Staging
Current Biomarkers / Profiles
Local invasion clinical stage, PSA, profiles for upstaging and
extracapsular extension Gleason Score, upgrading
seminal vesicle invasion % positive core, imaging
Positive lymph nodes imaging, PSA predictive:
Distant metastases Oncotype DX, Prolaris,
ProMark
Need: confirmatory markers
Moschini M, et al., BMC Med. 2016 Apr 4;14:67.
Watson MJ. et al., Future Oncol. 2016 Nov;12(21):2417-2430.
Brown JE. Et al., Neoplasia. 2010 Sep;12(9):685-96.
Wei RJ. Et al., Genet Mol Res. 2016 3;15(2).
OPG, ALP, DPD, PSA
TRAP5b, ICTP, BSPSecondary Staging (after radical prostatectomy / radiation therapy)
Recurrent disease PSA , imaging predictive:
local Oncotype DX, Prolaris,
metastases ProMark, Decipher
confirmatory: CTCs, ctDNA

4. Biomarkers vs Imaging
PROGNOSIS
GRADE
STAGE
PSA
Gleason
Imaging
% positive core
DRE
RECURRENCE
METASTASIS
SURVIVAL
UPGRADING
Beyond staging
1) Can we add molecular markers to complement imaging analyses?
2) Can we identify novel imaging targets from our molecular profiles?
Imaging modalities: Beyond technical issues
- heterogeneity within and between tumors
- molecular characteristics of the tumor

5. CIRCULATING TUMOR
CELLS
Urine
Serum
CELL-FREE
RNA
Cancer Research: Liquid biopsy
PROTEIN
METABOLITES
EXOSOMES
(exoRNA)
(exoPROTEINS)
(exoDNA)
CIRCULATING
TUMOR
DNA

6. Cancer Research: Liquid biopsy: Molecular characteristics and heterogeneity
McDaniel AS et al., BJUI 2016
Jiang R. et al., Oncotarget.
2015 Dec 29;6(42):44781-93.
Whole Genome
Sequencing of CTCs
Targeted sequencing
of circulating tumor
DNA

7. Biomarkers: Novel imaging markers
Not organ-specific
(18F)-FD-Glucose
(18F)-Choline
(11C)-Acetate
Tc-99m-MDP
18F-Sodium
Radium-223
Targeted
Bombesin
PSMA-Ab / antagonist
Testosteron
MDV3100
anti-γH2AX-TAT
Olaparib
CXCR4-Ab / antagonist
uPAR antagonist
AR
PARP
H2AX
AR
GRPR
PSMA
CXCR4
Can we identify novel imaging targets from our molecular profiles?
Novel targets:
ERG inhibitors; TMPRSS2; STEAP; ANPEP; PPAP2A; novel metabolites, and more
uPAR

8. Biomarkers vs Imaging: The next steps
CTCs
Exosomes
cfDNA
IMAGING
MOLECULAR
MARKERS
COMPLEMENTARY
PRESENCE, LOCATION AND CHARACTERISTICS
OF METASTASES
PATIENT STRATIFICATION
NOVEL IMAGING TARGETS