The TMPRSS2:ERG fusion and response to androgen deprivation therapy for prostate cancer.
BACKGROUND
In the United States, half of men with prostate cancer harbor the androgen-regulated gene fusion TMPRSS2:ERG. We hypothesized that men with TMPRSS2:ERG positive tumors are more responsive to androgen deprivation therapy (ADT).


METHODS
We studied a cohort of 239 men with prostate cancer from the Physicians' Health Study and Health Professionals Follow-up Study who received ADT during their disease course. Fusion status was assessed on available tumor tissue by immunohistochemistry for ERG protein expression. We used Cox models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for assessment of prostate cancer-specific mortality after ADT initiation.


RESULTS
Roughly half of the men had stage T3 or higher tumors at diagnosis and 39% had Gleason 8-10 tumors. During an average follow up of 10.2 years, 42 men died from prostate cancer. There was a non-significant inverse association between positive fusion status and time to death from prostate cancer after ADT (multivariable HR: 0.76; 95% CI: 0.40-1.45). Harboring the TMPRSS2:ERG fusion was associated with a statistically significant lower risk of prostate cancer mortality among men who were treated with orchiectomy (multivariable HR: 0.13; 95% CI: 0.03-0.62), based on 15 events.


CONCLUSIONS
Our results, combined with those from earlier studies, provide suggestive evidence that men with TMPRSS2:ERG positive tumors may have longer prostate cancer survival after ADT. Larger cohorts are needed for more robust results and to assess whether men with tumors harboring the fusion benefit from treatment with ADT in the (neo) adjuvant or metastatic setting specifically.
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
Rebecca E
RE
Graff
Andreas
A
Pettersson
Rosina T
RT
Lis
Natalie
N
DuPre
Kristina M
KM
Jordahl
Elizabeth
E
Nuttall
Jennifer R
JR
Rider
Michelangelo
M
Fiorentino
Howard D
HD
Sesso
Stacey A
SA
Kenfield
Massimo
M
Loda
Edward L
EL
Giovannucci
Bernard
B
Rosner
Paul L
PL
Nguyen
Christopher J
CJ
Sweeney
Lorelei A
LA
Mucci
D000368:Aged; D015331:Cohort Studies; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D057466:Nonsteroidal Anti-Androgens / Q000627:therapeutic use*; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011795:Surveys and Questionnaires; D016019:Survival Analysis
D057466:Nonsteroidal Anti-Androgens; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human
TMPRSS2:ERG; androgen deprivation therapy; gene fusion; prognosis; prostate cancer