Assessment of long-term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy.
BACKGROUND
In men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy.


METHODS
The authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score-dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided.


RESULTS
Incorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust with respect to the model parameters.


CONCLUSIONS
The use of PCA3 or T2:ERG testing for repeat biopsy decisions can substantially reduce the number of biopsies without significantly affecting 10-year survival.
Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, Michigan.
Selin
S
Merdan
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.|Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan.
Scott A
SA
Tomlins
Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, Michigan.
Christine L
CL
Barnett
Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan.
Todd M
TM
Morgan
Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan.
James E
JE
Montie
Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan.
John T
JT
Wei
Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, Michigan.|Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan.
Brian T
BT
Denton
D000368:Aged; D000951:Antigens, Neoplasm / Q000652:urine*; D001706:Biopsy; D050939:Gene Fusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000652:urine; D011994:Recombinant Proteins / Q000652:urine; D012697:Serine Endopeptidases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
D000951:Antigens, Neoplasm; C072312:ERG protein, human; D011994:Recombinant Proteins; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C479341:prostate cancer antigen 3, human; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; D017430:Prostate-Specific Antigen
TMPRSS2-ERG; prostate cancer; prostate cancer antigen 3; repeat biopsy; serine 2-ETS-related gene fusion; survival; transmembrane protease; urinary biomarkers