Table 1.
Selected biomarkers tested with prostate cancer radiotherapy.
| Biomarker Reference |
Treatment/follow-up time | Assay | BF | LF | DM | PCSS | OS | Comments |
|---|---|---|---|---|---|---|---|---|
| (i) PROTEIN | ||||||||
| p53 overexpression | ||||||||
| Grignon et al. (27) | RT vs. RT + STAD/5 years | IHC | NR | − | + | + | + | RTOG 86-10; pre-PSA era |
| Che et al. (28) | LTAD + RT vs. RT + STAD/5.9 years | − | − | + | + | − | RTOG 92-02; adverse for STAD | |
| Vergis et al. (29) | RT + STAD/7 years | − | NR | NR | NR | NR | Not prognostic on MV; RT dose-escalation study | |
| Scherr et al. (30) | RT/2.1 years | + | NR | NR | NR | NR | Adverse; see also data on BCL-2; short follow-up time | |
| Ritter et al. (31) | RT/5.1 years | + | NR | NR | NR | NR | Adverse following conformal RT | |
| D’Amico et al. (32) | RT + STAD/6.9 years | + | NR | NR | NR | NR | Adverse following RT ± AD | |
| Loss of p16INK4a | ||||||||
| Chakravarti et al. (33) | RT vs. RT + STAD/8.9 years | IHC | NR | + | + | + | − | RTOG 86-10; adverse |
| Chakravarti et al. (34) | LTAD + RT vs. RT + STAD/6.3 years | − | − | + | + | − | RTOG 92-02; p16 expression adverse for STAD (suggests use of LTAD in p16Hi cases) | |
| Loss of pRB | ||||||||
| Chakravarti et al. (33) | RT vs. RT + STAD/8.9 years | IHC | NR | − | − | + | − | RTOG 86-10; loss of pRB adverse |
| Ki-67 overexpression | ||||||||
| Li et al. (35) | RT vs. RT + STAD/9 years | IHC | NR | NR | + | + | − | RTOG 86-10; High Ki-67 adverse |
| Khor et al. (36) | LTAD + RT vs. RT + STAD/9.3 years | NR | NR | + | + | + | RTOG 92-02; High Ki-67 adverse; see also data on MDM2 | |
| Pollack et al. (37) | LTAD + RT vs. RT + STAD/8 years | + | + | + | + | + | RTOG 92-02; High Ki-67 adverse (continuous variable) | |
| Parker et al. (38) | SRT/6.2 years | + | NR | NR | NR | NR | High Ki-67 adverse following SRT | |
| Cowen et al. (39) | RT/5 years | + | NR | NR | NR | NR | High Ki-67 adverse | |
| Scalzo et al. (40) | RT/NA | + | NR | NR | NR | NR | High Ki-67 adverse | |
| DNA-PKcs | ||||||||
| Bouchaert et al. (41) | RT | IHC | + | NR | NR | NR | NR | DNA-PKcs adverse |
| MDM2 overexpression | ||||||||
| Khor et al. (42) | LTAD + RT vs. RT + STAD/9.3 years | IHC | − | − | + | − | + | RTOG 92-02; also adverse when combined with Ki-67 |
| Vergis et al. (29) | RT + STAD/7 years | − | NR | NR | NR | NR | Not prognostic on MV; RT dose-escalation study | |
| Bcl-2 and Bax overexpression | ||||||||
| Khor et al. (43) | RT vs. RT + STAD/6.7 years | IHC | NR | − | − | − | − | RTOG 86-10; Bcl-2 and Bax not prognostic |
| Khor et al. (44) | LTAD + RT vs. RT + STAD/10.5 years | − | − | − | − | − | RTOG 92-02, negative Bcl-2/normal Bax adverse | |
| Scherr et al. (30) | RT/2.1 years | + | NR | NR | NR | NR | Bcl-2 adverse, see also data on p53; short follow-up time | |
| Vergis et al. (29) | RT + STAD/7 years | + | NR | NR | NR | NR | Bcl-2 adverse (suggests benefit with dose escalation) | |
| Pollack et al. (45) | RT/5.1 years | + | NR | NR | NR | NR | Bcl-2 and Bax adverse on MV | |
| Bylund et al. (46) | RT/6.4 years | NR | NR | NR | + | − | Bcl-2 related to favorable outcome | |
| AR CAG repeats | ||||||||
| Abdel-Wahab et al. (47) | RT vs. RT + STAD/NA | flow cytometry | + | − | − | − | − | AR CAG repeats was not prognostic (suggests benefit with RT + STAD if short CAG repeats) |
| COX-2 | ||||||||
| Khor et al. (48) | LTAD + RT vs. RT + STAD/8.9 years | IHC | + | − | + | − | − | RTOG 92-02; COX-2 expression was adverse |
| STAT3 | ||||||||
| Torres-Roca et al. (49) | RT vs. RT + STAD/8.1 years | IHC | NR | − | + | − | − | RTOG 86-10; low levels of activated Stat3 was adverse |
| VEGF | ||||||||
| Green et al. (50) | RT/5.3 years | IHC | − | NR | − | + | − | VEGF was prognostic |
| Vergis et al. (51) | RT + STAD/7 years | + | NR | NR | NR | NR | VEGF was prognostic | |
| Weber et al. (52) | RT vs. RT + STAD/8.1 years | − | NR | NR | NR | NR | VEGF was not prognostic | |
| HIF-1 | ||||||||
| Vergis et al. (51) | RT + STAD/7 years | IHC | + | NR | NR | NR | NR | HIF1 α was adverse |
| Weber et al. (52) | RT vs. RT + STAD/8.1 years | + | NR | NR | NR | NR | HIF1α expression was associated to favorable outcome | |
| EGFR | ||||||||
| Weber et al. (52) | RT vs. RT + STAD/8.1 years | IHC | + | NR | NR | NR | NR | EGFR expression adverse |
| Osteopontin | ||||||||
| Vergis et al. (51) | RT + STAD/7 years | IHC | − | NR | NR | NR | NR | Osteopontin was not prognostic |
| Thoms et al. (53) | RT/NR | Elisa | − | NR | NR | NR | NR | Plasma osteopontin was not prognostic – OPN tested 1 year after treatment |
| PKA | ||||||||
| Pollack et al. (54) | LTAD + RT vs. RT + STAD/10.1 years | IHC | + | + | + | − | − | RTOG 92-02; PKA expression adverse for LTAD |
| Khor et al. (55) | RT vs. RT + STAD/12.2 years | + | + | + | − | NR | RTOG 86-10; PKA expression adverse | |
| ERG | ||||||||
| Dal Pra et al. (56) | RT/6.2 years | IHC | − | NR | NR | NR | NR | ERG status was not prognostic |
| (ii) DNA | ||||||||
| DNA ploidy | ||||||||
| Pollack et al. (57) | RT vs. RT + STAD/9 years | Image analysis of Feulgen stained tissue sections | NR | NR | − | NR | + | RTOG 86-10; non-diploid tumors was adverse |
| Cyp3A4 polymorphisms | ||||||||
| Roach et al. (58) | LTAD + RT vs. RT + STAD/NA | PCR based detection | − | NR | NR | NR | − | Cyp3A4*1B polymorphism was not prognostic, regardless of race |
| c-MYC ± PTEN | ||||||||
| Zafarana et al. (19) | RT/6.7 years | aCGH + FISH | + | NR | NR | NR | NR | c-MYC gain alone or combined with PTEN loss was adverse |
| NKX3.1 ± c-MYC | ||||||||
| Locke et al. (21) | RT/6.7 years | aCGH + FISH | + | NR | NR | NR | NR | NKX3.1 haploinsufficiency alone or combined with c-MYC gain was adverse |
| StAR; HSD17B2 | ||||||||
| Locke et al. (20) | RT/6.7 years | aCGH + FISH | + | NR | NR | NR | NR | Allelic losses of the loci containing StAR and HSD17B2 were adverse |
| TMPRSS2-ERG | ||||||||
| Dal Pra et al. (56) | RT/6.2 years | aCGH | − | NR | NR | NR | NR | TMPRSS2-ERG status was not prognostic |
| NBN | ||||||||
| Berlin et al. (59) | RT/6.7 years | aCGH | + | NR | NR | NR | NR | NBN gain predicted for decreased BF in RT, but not in RadP patients |
| Toronto | ||||||||
| Lalonde et al (60) | RT/6.7 years | 100 loci DNA signature | + | NR | NR | NR | NR | Combined indices of genomic instability and hypoxia predict BF and early BF (≤18 months). |
| (iii) RNA | ||||||||
| Myriad Genetics Prolaris Score™ | ||||||||
| Freedland et al. (61) | RT + ADT/4.8 years | 31-gene RNA expression signature – CCP genes (RT-PCR) | + | NR | NR | NR | NR | RNA based diagnostic assay (CCP score) was prognostic after EBRT |
| GenomeDx Biosciences Decipher™ | ||||||||
| Den et al. (62) | Post-operative RT/8 years* | 22-gene RNA expression signature (gene expression microarray) | NR | NR | + | NR | NR | Genomic classifier is prognostic for distant metastasis |
Importance of biomarker: + is statistically significant (p < 0.05) as independent prognostic marker on multivariate analysis, − is not significant.
NR, not reported; BF, biochemical failure; LF, local failure; DM, distant metastasis; PCSS, prostate cancer specific survival; OS, overall survival; IHC, immunohistochemistry; LTAD, long-term androgen deprivation; PC, prostate cancer; RT, radiotherapy; SRT, salvage radiotherapy; aCGH, array comparative genome hybridization; FISH, fluorescence in situ hybridization; MV, multivariate analysis; NA, not available; median follow-up after radiotherapy; RadP, radical prostatectomy.