Rational approach to implementation of prostate cancer antigen 3 into clinical care

Abstract

Background Prostate cancer gene 3 (PCA3) encodes a prostate-specific messenger RNA (mRNA) that serves as the target for a novel urinary molecular assay for prostate cancer detection. Our objective is to evaluate the ability of PCA3 in addition to serum prostate-specific antigen (PSA) to predict cancer detection by extended template biopsy. Methods From September 2006 to December 2007, whole urine samples were collected after attentive digital rectal exam from 187 men prior to ultrasound-guided 12-core prostate biopsy in a urology outpatient clinic. Urine PCA3/PSA mRNA ratio scores were measured within one month and serum PSA within six months of biopsy. These were related to cancer positivity on biopsy. Results Overall, 87/187 (46.5%) biopsies were positive for cancer. Sensitivity and specificity of PCA3 score ≥35 for positive biopsy were 52.9% and 80.0%; positive and negative predictive values were 69.7% and 66.1%. Using receiver operating characteristic curve (ROC) analysis, PSA alone resulted in an area under the curve (AUC) of 0.63 for prostate cancer detection; PSA + PCA3 score resulted in an AUC of 0.71. The likelihood of prostate cancer detection rose with increasing PCA3 score ranges (p>0.0001), providing possible PCA3 score parameters for stratification into low, moderate, high, and very high risk groups for biopsy positivity. Conclusion Adding PCA3 to serum PSA improves prostate cancer prediction. Use of PCA3 in a clinical setting may help risk-stratify patients for biopsy and cancer detection, although a large-scale validation study is needed to address assay standardization, optimal cut-off values and appropriate patient populations.

Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes?

“…However, 12 additional studies included matched results of PCA3 and the comparators but enrolled men with both initial and repeat biopsies or they did not report biopsy history. 10,11,[35][36][37][38][39][40][41][42][43][44] Most often, the results from these studies were not stratified by biopsy history.…”

“…Fifteen studies [9][10][11]30,32,[34][35][36][37][38][39][40][41][42][43]46 reported AUC estimates for tPSA and PCA3 in the same population. Overall, 13 [9][10][11]30,32,34,35,37,38,[40][41][42]46 of the15 studies found that the AUC of PCA3 was higher than that of tPSA.…”

“…Seven studies 9,33,36,37,39,40,43 reported the sensitivity and specificity of PCA3 at a cutoff of 35. Six 9,33,36,37,40,43 of the seven studies reported a higher sensitivity in PCA3.…”

Evaluación del test PCA3 para el diagnóstico de cáncer de próstata: revisión sistemática y metanálisis

“…Los estudios incluidos finalmente, tras la lectura a texto completo, fueron 14 estudios de pruebas diagnó sticas 3,7,8,[15][16][17][18][19][20][21][22][23][24][25] que cumplieron los criterios de inclusió n ( fig. 1) y un informe de una agencia de evaluació n de tecnología sanitaria elaborado por )National Horizon Scanning Centre* 26 que sintetizaba resultados varios estudios en los que en todos se obtenía buena especificidad y sensibilidad.…”

“…En todos los trabajos se describían los criterios de selecció n de pacientes y estos eran representativos de toda la població n. El gold standard utilizado (biopsia) fue adecuado en todos los casos y este siempre era comparado con la intervenció n. En 5 artículos la realizació n de las 2 pruebas no se realizó de manera simultá nea [15][16][17]20,24 y en uno el gold standard no se aplicó a todos los pacientes 20 . El cegamiento de los investigadores para la interpretació n de la prueba de referencia solo se registró 2 estudios 7,19 .…”